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Journal articles on the topic 'In Vitro Compartmentalised Self Replication'

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Published: 20 October 2023

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1

Bansho, Yohsuke, Taro Furubayashi, Norikazu Ichihashi, and Tetsuya Yomo. "Host–parasite oscillation dynamics and evolution in a compartmentalized RNA replication system." Proceedings of the National Academy of Sciences 113, no. 15 (2016): 4045–50. http://dx.doi.org/10.1073/pnas.1524404113.

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To date, various cellular functions have been reconstituted in vitro such as self-replication systems using DNA, RNA, and proteins. The next important challenges include the reconstitution of the interactive networks of self-replicating species and investigating how such interactions generate complex ecological behaviors observed in nature. Here, we synthesized a simple replication system composed of two self-replicating host and parasitic RNA species. We found that the parasitic RNA eradicates the host RNA under bulk conditions; however, when the system is compartmentalized, a continuous osci

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2

Dramé-Maigné, Adèle, Anton S. Zadorin, Iaroslava Golovkova, and Yannick Rondelez. "Quantifying the Performance of Micro-Compartmentalized Directed Evolution Protocols." Life 10, no. 2 (2020): 17. http://dx.doi.org/10.3390/life10020017.

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High-throughput, in vitro approaches for the evolution of enzymes rely on a random micro-encapsulation to link phenotypes to genotypes, followed by screening or selection steps. In order to optimise these approaches, or compare one to another, one needs a measure of their performance at extracting the best variants of a library. Here, we introduce a new metric, the Selection Quality Index (SQI), which can be computed from a simple mock experiment, performed with a known initial fraction of active variants. In contrast to previous approaches, our index integrates the effect of random co-encapsu

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3

Mulaj, Mentor, Tatiana Miti, and Martin Muschol. "Self-Replication of Transthyretin Amyloid Aggregates from Native Tetramers in vitro." Biophysical Journal 108, no. 2 (2015): 45a. http://dx.doi.org/10.1016/j.bpj.2014.11.280.

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4

Wang, Li-juan, Hou-xiu Wang, Longhe Jiang, and Chun-yang Zhang. "Development of an in Vitro Autocatalytic Self-Replication System for Biosensing Application." ACS Sensors 3, no. 12 (2018): 2675–83. http://dx.doi.org/10.1021/acssensors.8b01171.

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5

Rupp, Brigitte, Zsolt Ruzsics, Torsten Sacher, and Ulrich H. Koszinowski. "Conditional Cytomegalovirus Replication In Vitro and In Vivo." Journal of Virology 79, no. 1 (2005): 486–94. http://dx.doi.org/10.1128/jvi.79.1.486-494.2005.

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ABSTRACT We have established a conditional gene expression system for cytomegalovirus which allows regulation of genes independently from the viral replication program. Due to the combination of all elements required for regulated expression in the same viral genome, conditional viruses can be studied in different cell lines in vitro and in the natural host in vivo. The combination of a self-sufficient tetracycline-regulated expression cassette and Flp recombinase-mediated insertion into the viral genome allowed fast construction of recombinant murine cytomegaloviruses carrying different condi

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6

Hwang, Yung, Melinda Futran, Daniel Hidalgo, Divya Ramalingam Iyer, Nicholas Rhind, and Merav Socolovsky. "Global Increase in Replication Fork Speed during a p57KIP2-Regulated Erythroid Cell Fate Switch." Blood 128, no. 22 (2016): 698. http://dx.doi.org/10.1182/blood.v128.22.698.698.

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Abstract Cell cycle regulators are increasingly implicated in cell fate decisions such as the acquisition or loss of pluripotency and self-renewal potential. The cell cycle mechanisms that regulate these cell fate decisions are largely unknown. Here we studied an S phase- dependent cell fate switch in the erythroid fetal liver, in which murine early erythroid progenitors transition in vivo from a self-renewal state into a phase of active erythroid gene transcription and concurrent maturational cell divisions. In the fetal liver, this transition corresponds to the transition from subset S0 (CD7

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7

Sugiyama, Kazuo, Kenji Suzuki, Takahide Nakazawa, et al. "Genetic Analysis of Hepatitis C Virus with Defective Genome and Its Infectivity in Vitro." Journal of Virology 83, no. 13 (2009): 6922–28. http://dx.doi.org/10.1128/jvi.02674-08.

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ABSTRACT Replication and infectivity of hepatitis C virus (HCV) with a defective genome is ambiguous. We molecularly cloned 38 HCV isolates with defective genomes from 18 patient sera. The structural regions were widely deleted, with the 5′ untranslated, core, and NS3-NS5B regions preserved. All of the deletions were in frame, indicating that they are translatable to the authentic terminus. Phylogenetic analyses showed self-replication of the defective genomes independent of full genomes. We generated a defective genome of chimeric HCV to mimic the defective isolate in the serum. By using this

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8

Zitzmann, Carolin, Christopher Dächert, Bianca Schmid, et al. "Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies." PLOS Computational Biology 19, no. 4 (2023): e1010423. http://dx.doi.org/10.1371/journal.pcbi.1010423.

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Plus-strand RNA viruses are the largest group of viruses. Many are human pathogens that inflict a socio-economic burden. Interestingly, plus-strand RNA viruses share remarkable similarities in their replication. A hallmark of plus-strand RNA viruses is the remodeling of intracellular membranes to establish replication organelles (so-called “replication factories”), which provide a protected environment for the replicase complex, consisting of the viral genome and proteins necessary for viral RNA synthesis. In the current study, we investigate pan-viral similarities and virus-specific differenc

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9

Jain, Bhawana, Amita Jain, Om Prakash, et al. "In-vitro validation of self designed siRNA targeting non-structural 1 gene of Influenza A virus." South Asian Journal of Experimental Biology 4, no. 6 (2015): 315–22. http://dx.doi.org/10.38150/sajeb.4(6).p315-322.

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The genomic variability makes Influenza A virus (IAV) difficult to be con-trolled by existing vaccines or anti-influenza drugs. Viral gene targeting siRNA induces the RNAi mechanism in the host and silents the gene by cleaving mRNA. Objective was to develop siRNA targeting non-structural 1 gene and to validate its efficiency in vitro. siRNA was designed rationally, targeting the most conserved region (delineated with the help of multiple sequence align-ment) of NS1 gene of IAV strains. To choose the most efficient siRNA, three levels screening method was developed. Ultimately one siRNA duplex

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10

Bourne, Christina, Sejin Lee, Bollu Venkataiah, et al. "Small-Molecule Effectors of Hepatitis B Virus Capsid Assembly Give Insight into Virus Life Cycle." Journal of Virology 82, no. 20 (2008): 10262–70. http://dx.doi.org/10.1128/jvi.01360-08.

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ABSTRACT The relationship between the physical chemistry and biology of self-assembly is poorly understood, but it will be critical to quantitatively understand infection and for the design of antivirals that target virus genesis. Here we take advantage of heteroaryldihydropyrimidines (HAPs), which affect hepatitis B virus (HBV) assembly, to gain insight and correlate in vitro assembly with HBV replication in culture. Based on a low-resolution crystal structure of a capsid-HAP complex, a closely related series of HAPs were designed and synthesized. These differentially strengthen the associati

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11

Titolo, Steve, Alex Pelletier, Anne-Marie Pulichino, et al. "Identification of Domains of the Human Papillomavirus Type 11 E1 Helicase Involved in Oligomerization and Binding to the Viral Origin." Journal of Virology 74, no. 16 (2000): 7349–61. http://dx.doi.org/10.1128/jvi.74.16.7349-7361.2000.

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ABSTRACT The E1 helicase of papillomavirus is required, in addition to host cell DNA replication factors, during the initiation and elongation phases of viral episome replication. During initiation, the viral E2 protein promotes the assembly of enzymatically active multimeric E1 complexes at the viral origin of DNA replication. In this study we used the two-hybrid system and chemical cross-linking to demonstrate that human papillomavirus type 11 (HPV11) E1 can self-associate in yeast and form hexamers in vitro in a reaction stimulated by single-stranded DNA. Self-association in yeast was most

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12

Woerman, Amanda L., Sabeen A. Kazmi, Smita Patel, et al. "Familial Parkinson’s point mutation abolishes multiple system atrophy prion replication." Proceedings of the National Academy of Sciences 115, no. 2 (2017): 409–14. http://dx.doi.org/10.1073/pnas.1719369115.

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In the neurodegenerative disease multiple system atrophy (MSA), α-synuclein misfolds into a self-templating conformation to become a prion. To compare the biological activity of α-synuclein prions in MSA and Parkinson’s disease (PD), we developed nine α-synuclein−YFP cell lines expressing point mutations responsible for inherited PD. MSA prions robustly infected wild-type, A30P, and A53T α-synuclein–YFP cells, but they were unable to replicate in cells expressing the E46K mutation. Coexpression of the A53T and E46K mutations was unable to rescue MSA prion infection in vitro, establishing that

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13

Borghesi, Lisa, Qi Yang, and Brandt Esplin. "Cell intrinsic E47 is required for stem cell self-renewal and differentiation but is dispensable for short-term myeloid development (36.2)." Journal of Immunology 184, no. 1_Supplement (2010): 36.2. http://dx.doi.org/10.4049/jimmunol.184.supp.36.2.

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Abstract The immune system is constantly replenished by a rare population of hematopoietic stem cells (HSC) residing in the bone marrow of adult organisms. E-proteins, the widely expressed basic helix-loop-helix (bHLH) transcription factors, appear to contribute to HSC activity, but their specific cell intrinsic functions remain undefined. In contrast to a recent report, we show that E47 is dispensable for the short-term myeloid differentiation of HSCs. In our quantitative assays, E47 deficient progenitors show competent myeloid production in vitro and in vivo as well as under burden of a path

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14

Risager, Peter Christian, Ulrik Fahnøe, Maria Gullberg, Thomas Bruun Rasmussen, and Graham J. Belsham. "Analysis of classical swine fever virus RNA replication determinants using replicons." Journal of General Virology 94, no. 8 (2013): 1739–48. http://dx.doi.org/10.1099/vir.0.052688-0.

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Self-replicating RNAs (replicons), with or without reporter gene sequences, derived from the genome of the Paderborn strain of classical swine fever virus (CSFV) have been produced. The full-length viral cDNA, propagated within a bacterial artificial chromosome, was modified by targeted recombination within Escherichia coli. RNA transcripts were produced in vitro and introduced into cells by electroporation. The translation and replication of the replicon RNAs could be followed by the accumulation of luciferase (from Renilla reniformis or Gaussia princeps) protein expression (where appropriate

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15

Sekulovic, Sanja, Vala Gylfadottir, Irma Vulto, et al. "Prolonged self-renewal activity unmasks telomerase control of telomere homeostasis and function of mouse hematopoietic stem cells." Blood 118, no. 7 (2011): 1766–73. http://dx.doi.org/10.1182/blood-2010-11-319632.

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Abstract Strategies for expanding hematopoietic stem cells (HSCs) could have significant utility for transplantation-based therapies. However, deleterious consequences of such manipulations remain unknown. Here we examined the impact of HSC self-renewal divisions in vitro and in vivo on their subsequent regenerative and continuing ability to sustain blood cell production in the absence of telomerase. HSC expansion in vitro was obtained using a NUP98-HOXA10hd transduction strategy and, in vivo, using a serial transplant protocol. We observed ∼ 10kb telomere loss in leukocytes produced in second

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16

Khromykh, Alexander A., Natasha Kondratieva, Jean-Yves Sgro, Ann Palmenberg, and Edwin G. Westaway. "Significance in Replication of the Terminal Nucleotides of the Flavivirus Genome." Journal of Virology 77, no. 19 (2003): 10623–29. http://dx.doi.org/10.1128/jvi.77.19.10623-10629.2003.

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ABSTRACT Point mutations that resulted in a substitution of the conserved 3′-penultimate cytidine in genomic RNA or the RNA negative strand of the self-amplifying replicon of the Flavivirus Kunjin virus completely blocked in vivo replication. Similarly, substitutions of the conserved 3′-terminal uridine in the RNA negative or positive strand completely blocked replication or caused much-reduced replication, respectively. The same preference for cytidine in the 3′-terminal dinucleotide was noted in reports of the in vitro activity of the RNA-dependent RNA polymerase (RdRp) for the other genera

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17

Park, Mi-Young, Young-Eui Kim, Myong-Rang Seo, Jae-Rin Lee, Chan Hee Lee, and Jin-Hyun Ahn. "Interactions among Four Proteins Encoded by the Human Cytomegalovirus UL112-113 Region Regulate Their Intranuclear Targeting and the Recruitment of UL44 to Prereplication Foci." Journal of Virology 80, no. 6 (2006): 2718–27. http://dx.doi.org/10.1128/jvi.80.6.2718-2727.2006.

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ABSTRACT Four phosphoproteins, of 34, 43, 50, and 84 kDa, with common amino termini are synthesized via alternative splicing from the UL112-113 region of the human cytomegalovirus genome. Although genetic studies provided evidence that both the UL112 and UL113 loci in the viral genome are required for efficient viral replication, whether the four proteins play specific roles or cooperate in replication is not understood. Here we present evidence, using in vitro and in vivo coimmunoprecipitation assays, that the four UL112-113 proteins both self-interact and interact with each other. A mapping

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18

Serio, Tricia R., Anil G. Cashikar, Anthony S. Kowal, George J. Sawicki, and Susan L. Lindquist. "Self-perpetuating changes in Sup35 protein conformation as a mechanism of heredity in yeast." Biochemical Society Symposia 68 (August 1, 2001): 35–43. http://dx.doi.org/10.1042/bss0680035.

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Recently, a novel mode of inheritance has been described in the yeast Saccharomyces cerevisiae. The mechanism is based on the prion hypothesis, which posits that self-perpetuating changes in the conformation of single protein, PrP, underlie the severe neurodegeneration associated with the transmissible spongiform enchephalopathies in mammals. In yeast, two prions, [URE3] and [PSI+], have been identified, but these factors confer unique phenotypes rather than disease to the organism. In each case, the prion-associated phenotype has been linked to alternative conformations of the Ure2 and Sup35

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19

Han, Dongran, Xiaodong Qi, Cameron Myhrvold, et al. "Single-stranded DNA and RNA origami." Science 358, no. 6369 (2017): eaao2648. http://dx.doi.org/10.1126/science.aao2648.

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Self-folding of an information-carrying polymer into a defined structure is foundational to biology and offers attractive potential as a synthetic strategy. Although multicomponent self-assembly has produced complex synthetic nanostructures, unimolecular folding has seen limited progress. We describe a framework to design and synthesize a single DNA or RNA strand to self-fold into a complex yet unknotted structure that approximates an arbitrary user-prescribed shape. We experimentally construct diverse multikilobase single-stranded structures, including a ~10,000-nucleotide (nt) DNA structure

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20

Gao, Hong-Qiang, Stefan G. Sarafianos, Edward Arnold, and Stephen H. Hughes. "RNase H Cleavage of the 5′ End of the Human Immunodeficiency Virus Type 1 Genome." Journal of Virology 75, no. 23 (2001): 11874–80. http://dx.doi.org/10.1128/jvi.75.23.11874-11880.2001.

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ABSTRACT The synthesis of retroviral DNA is initiated near the 5′ end of the RNA. DNA synthesis is transferred from the 5′ end to the 3′ end of viral RNA in an RNase H-dependent step. In the case of human immunodeficiency virus type 1 (HIV-1) (and certain other retroviruses that have complex secondary structures at the ends of the viral RNA), there is the possibility that DNA synthesis can lead to a self-priming event that would block viral replication. The extent of RNase H cleavage must be sufficient to allow the strand transfer reaction to occur, but not so extensive that self-priming occur

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21

Kato, Takanobu, Takuya Matsumura, Theo Heller, et al. "Production of Infectious Hepatitis C Virus of Various Genotypes in Cell Cultures." Journal of Virology 81, no. 9 (2007): 4405–11. http://dx.doi.org/10.1128/jvi.02334-06.

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ABSTRACT A unique hepatitis C virus (HCV) strain JFH-1 has been shown to replicate efficiently in cell culture with production of infectious HCV. We previously developed a DNA expression system containing HCV cDNA flanked by two self-cleaving ribozymes to generate HCV particles in cell culture. In this study, we produced HCV particles of various genotypes, including 1a (H77), 1b (CG1b), and 2a (J6 and JFH-1), in the HCV-ribozyme system. The constructs also contain the secreted alkaline phosphatase gene to control for transfection efficiency and the effects of culture conditions. After transfec

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22

Zhang, Chaozheng, Yueyong Liu, Liyue Liu та ін. "Rice black streaked dwarf virus P9-1, an α-helical protein, self-interacts and forms viroplasms in vivo". Journal of General Virology 89, № 7 (2008): 1770–76. http://dx.doi.org/10.1099/vir.0.2008/000109-0.

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Replication and assembly of viruses from the family Reoviridae are thought to take place in discrete cytoplasmic inclusion bodies, commonly called viral factories or viroplasms. Rice black streaked dwarf virus (RBSDV) P9-1, a non-structural protein, has been confirmed to accumulate in these intracellular viroplasms in infected plants and insects. However, little is known about its exact function. In this study, P9-1 of RBSDV-Baoding was expressed in Escherichia coli as a His-tagged fusion protein and analysed using biochemical and biophysical techniques. Mass spectrometry and circular dichrois

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23

Hricik, Todd, Anna Sophia McKenney, Ross L. Levine, et al. "Transcriptosome and Phospho-Proteomic Analyses of Erythroblasts Expanded in Vitro From Normal Donors (ND) and From Patients with Polycythemia Vera (PV)." Blood 120, no. 21 (2012): 2860. http://dx.doi.org/10.1182/blood.v120.21.2860.2860.

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Abstract Abstract 2860 Expansion of EBs is observed when cells from ND are cultured with the glucocorticoid receptor α(GRα) agonist dexamethasone (DXM). In addition, EBs can be cultured from patients with PV, a disease characterized by erythrocytosis, in the presence (+) or absence (−) of DXM (Varricchio et al. Blood. 2011;118:425). In cultures of ND, DXM induces expansion by inducing EBs into a reversible self-replication state and attenuating STAT5 activation mediated by the erythropoietin receptor (EPO-R). In cultures of PV, EB expansion is due to acquisition of a constitutive self-replicat

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24

van Leeuwen, Hans C., Chantal B. E. M. Reusken, Marko Roeten, et al. "Evolution of naturally occurring 5′ non-translated region variants of hepatitis C virus genotype 1b in selectable replicons." Journal of General Virology 85, no. 7 (2004): 1859–66. http://dx.doi.org/10.1099/vir.0.79924-0.

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Quasispecies shifts are essential for the development of persistent hepatitis C virus (HCV) infection. Naturally occurring sequence variations in the 5′ non-translated region (NTR) of the virus could lead to changes in protein expression levels, reflecting selective forces on the virus. The extreme 5′ end of the virus' genome, containing signals essential for replication, is followed by an internal ribosomal entry site (IRES) essential for protein translation as well as replication. The 5′ NTR is highly conserved and has a complex RNA secondary structure consisting of several stem–loops. This

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25

Driscoll, Mark D., and Stephen H. Hughes. "Human Immunodeficiency Virus Type 1 Nucleocapsid Protein Can Prevent Self-Priming of Minus-Strand Strong Stop DNA by Promoting the Annealing of Short Oligonucleotides to Hairpin Sequences." Journal of Virology 74, no. 19 (2000): 8785–92. http://dx.doi.org/10.1128/jvi.74.19.8785-8792.2000.

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ABSTRACT Understanding how viral components collaborate to convert the human immunodeficiency virus type 1 genome from single-stranded RNA into double-stranded DNA is critical to the understanding of viral replication. Not only must the correct reactions be carried out, but unwanted side reactions must be avoided. After minus-strand strong stop DNA (−sssDNA) synthesis, degradation of the RNA template by the RNase H domain of reverse transcriptase (RT) produces single-stranded DNA that has the potential to self-prime at the imperfectly base-paired TAR hairpin, making continued DNA synthesis imp

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26

Zufferey, Romain, Thomas Dull, Ronald J. Mandel, et al. "Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery." Journal of Virology 72, no. 12 (1998): 9873–80. http://dx.doi.org/10.1128/jvi.72.12.9873-9880.1998.

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ABSTRACT In vivo transduction of nondividing cells by human immunodeficiency virus type 1 (HIV-1)-based vectors results in transgene expression that is stable over several months. However, the use of HIV-1 vectors raises concerns about their safety. Here we describe a self-inactivating HIV-1 vector with a 400-nucleotide deletion in the 3′ long terminal repeat (LTR). The deletion, which includes the TATA box, abolished the LTR promoter activity but did not affect vector titers or transgene expression in vitro. The self-inactivating vector transduced neurons in vivo as efficiently as a vector wi

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27

Chen, Mingzhou, Tomoaki Ogino, and Amiya K. Banerjee. "Mapping and Functional Role of the Self-Association Domain of Vesicular Stomatitis Virus Phosphoprotein." Journal of Virology 80, no. 19 (2006): 9511–18. http://dx.doi.org/10.1128/jvi.01035-06.

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ABSTRACT The phosphoprotein (P protein) of vesicular stomatitis virus (VSV) is an essential subunit of the viral RNA-dependent RNA polymerase complex and plays a central role in viral transcription and replication. Using both the yeast two-hybrid system and coimmunoprecipitation assays, we confirmed the self-association of the P protein of Indiana serotype (Pind) and heterotypic interaction between Pind and the P protein of New Jersey serotype (Pnj). Furthermore, by using various truncation and deletion mutants of Pind, the self-association domain of the Pind protein was mapped to amino acids

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28

Schregel, Vera, Sabrina Auerochs, Ramona Jochmann, Katja Maurer, Thomas Stamminger, and Manfred Marschall. "Mapping of a self-interaction domain of the cytomegalovirus protein kinase pUL97." Journal of General Virology 88, no. 2 (2007): 395–404. http://dx.doi.org/10.1099/vir.0.82393-0.

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The human cytomegalovirus-encoded protein kinase pUL97 is a determinant of efficient virus replication and fulfils several regulatory functions. In particular, pUL97 interacts with and phosphorylates viral and cellular proteins. Substrate phosphorylation has regulatory consequences on viral replicative stages such as DNA synthesis, transcription and nuclear capsid egress. pUL97, in accordance with related herpesviral protein kinases, possesses strong autophosphorylation activity. Here, we demonstrate that pUL97 shows a pronounced potential to self-interact. Self-interaction of pUL97 is not dep

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29

Shuchat, Sholom, Gilad Yossifon, and Mahmoud Huleihel. "Perfusion in Organ-on-Chip Models and Its Applicability to the Replication of Spermatogenesis In Vitro." International Journal of Molecular Sciences 23, no. 10 (2022): 5402. http://dx.doi.org/10.3390/ijms23105402.

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Organ/organoid-on-a-chip (OoC) technologies aim to replicate aspects of the in vivo environment in vitro, at the scale of microns. Mimicking the spatial in vivo structure is important and can provide a deeper understanding of the cell–cell interactions and the mechanisms that lead to normal/abnormal function of a given organ. It is also important for disease models and drug/toxin testing. Incorporating active fluid flow in chip models enables many more possibilities. Active flow can provide physical cues, improve intercellular communication, and allow for the dynamic control of the environment

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30

Mears, Harriet V., Edward Emmott, Yasmin Chaudhry, Myra Hosmillo, Ian G. Goodfellow, and Trevor R. Sweeney. "Ifit1 regulates norovirus infection and enhances the interferon response in murine macrophage-like cells." Wellcome Open Research 4 (May 15, 2019): 82. http://dx.doi.org/10.12688/wellcomeopenres.15223.1.

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Background: Norovirus, also known as the winter vomiting bug, is the predominant cause of non-bacterial gastroenteritis worldwide. Disease control is predicated on a robust innate immune response during the early stages of infection. Double-stranded RNA intermediates generated during viral genome replication are recognised by host innate immune sensors in the cytoplasm, activating the strongly antiviral interferon gene programme. Ifit proteins (interferon induced proteins with tetratricopeptide repeats), which are highly expressed during the interferon response, have been shown to directly inh

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31

Pellerin, Marie, Edouard Hirchaud, Yannick Blanchard, Nicole Pavio, and Virginie Doceul. "Characterization of a Cell Culture System of Persistent Hepatitis E Virus Infection in the Human HepaRG Hepatic Cell Line." Viruses 13, no. 3 (2021): 406. http://dx.doi.org/10.3390/v13030406.

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Hepatitis E virus (HEV) is considered as an emerging global health problem. In most cases, hepatitis E is a self-limiting disease and the virus is cleared spontaneously without the need of antiviral therapy. However, immunocompromised individuals can develop chronic infection and liver fibrosis that can progress rapidly to cirrhosis and liver failure. The lack of efficient and relevant cell culture system and animal models has limited our understanding of the biology of HEV and the development of effective drugs for chronic cases. In the present study, we developed a model of persistent HEV in

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32

Kuwasaki, T. "Inhibition of human immunodeficiency virus 1 replication in vitro by a self-stabilized oligonucleotide with 2'-O-methyl-guanosine-uridine quadruplex motifs." Journal of Antimicrobial Chemotherapy 51, no. 4 (2003): 813–19. http://dx.doi.org/10.1093/jac/dkg174.

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33

Holec, Sara A. M., Jisoo Lee, Abby Oehler та ін. "The E46K mutation modulates α-synuclein prion replication in transgenic mice". PLOS Pathogens 18, № 12 (2022): e1010956. http://dx.doi.org/10.1371/journal.ppat.1010956.

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In multiple system atrophy (MSA), the α-synuclein protein misfolds into a self-templating prion conformation that spreads throughout the brain, leading to progressive neurodegeneration. While the E46K mutation in α-synuclein causes familial Parkinson’s disease (PD), we previously discovered that this mutation blocks in vitro propagation of MSA prions. Recent studies by others indicate that α-synuclein adopts a misfolded conformation in MSA in which a Greek key motif is stabilized by an intramolecular salt bridge between residues E46 and K80. Hypothesizing that the E46K mutation impedes salt br

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34

López, Lissett, Ana Urzainqui, Elvira Domínguez, and Juan Antonio García. "Identification of an N-terminal domain of the plum pox potyvirus CI RNA helicase involved in self-interaction in a yeast two-hybrid system." Journal of General Virology 82, no. 3 (2001): 677–86. http://dx.doi.org/10.1099/0022-1317-82-3-677.

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Potyvirus CI RNA helicase is a protein involved in RNA genome replication and virus movement. The protein aggregates in the cytoplasm of infected cells to form typical cylindrical inclusions. A yeast two-hybrid system was used to analyse interactions of the CI RNA helicase from plum pox potyvirus (PPV) with itself and with other viral proteins. No interactions could be detected of full-length CI protein with itself or with PPV P3/6K1, NIa, NIb or CP proteins. However, positive self-interactions were detected for N-terminal fragments of the CI protein, allowing the mapping of a CI–CI binding do

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35

Nahhas, Alaa F., and Thomas J. Webster. "Targeting the Conserved Sequence of the Substrate for the Proteinase of Severe-Acute-Respiratory-Syndrome-Coronavirus-2 (SARS-CoV-2) Using Nano-Networks: Efficacy, Stability, and No Cytotoxicity." Journal of Biomedical Nanotechnology 18, no. 4 (2022): 1158–63. http://dx.doi.org/10.1166/jbn.2022.3330.

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Herein, we designed a nano peptide that contains three important motifs for targeting the chemotrypsin-like cysteine protease (3CLpro) which is the enzyme responsible for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) replication. The novel nano peptide contains the Nap Phe-Phe motif that is responsible for peptide self-assembly, an octapeptide (Ser-Ala-Val-Leu-Gln-Ser-Gly-Phe) motif where the enzyme recognizes the substrate and induces enzyme sensitivity, and a tetrapeptide motif which is positively charged containing the peptide (Lys)4 that facilitates penetration into a cell.

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Petrucelli, Alex, Mahadevaiah Umashankar, Patricia Zagallo, Michael Rak, and Felicia Goodrum. "Interactions between Proteins Encoded within the Human CytomegalovirusUL133-UL138Locus." Journal of Virology 86, no. 16 (2012): 8653–62. http://dx.doi.org/10.1128/jvi.00465-12.

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We previously described a novel genetic locus within the ULb′ region of the human cytomegalovirus (HCMV) genome that, while dispensable for replication in fibroblasts, suppresses replication in hematopoietic progenitors and augments replication in endothelial cells. This locus, referred to as theUL133-UL138locus, encodes four proteins, pUL133, pUL135, pUL136, and pUL138. In this work, we have mapped the interactions among these proteins. An analysis of all pairwise interactions during transient expression revealed a robust interaction between pUL133 and pUL138. Potential interactions between p

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Joseph, Aviva, Jian Hua Zheng, Antonia Follenzi, et al. "Lentiviral Vectors Encoding Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Receptor Genes Efficiently Convert Peripheral Blood CD8 T Lymphocytes into Cytotoxic T Lymphocytes with Potent In Vitro and In Vivo HIV-1-Specific Inhibitory Activity." Journal of Virology 82, no. 6 (2008): 3078–89. http://dx.doi.org/10.1128/jvi.01812-07.

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ABSTRACT The human immunodeficiency virus type 1 (HIV-1)-specific CD8 cytotoxic T-lymphocyte (CTL) response plays a critical role in controlling HIV-1 replication. Augmenting this response should enhance control of HIV-1 replication and stabilize or improve the clinical course of the disease. Although cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection in immunocompromised patients can be treated by adoptive transfer of ex vivo-expanded CMV- or EBV-specific CTLs, adoptive transfer of ex vivo-expanded, autologous HIV-1-specific CTLs had minimal effects on HIV-1 replication, likely a con

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Le, Hang Phuong, Xiaoyan Ma, Jorge Vaquero, et al. "DSS1 and ssDNA regulate oligomerization of BRCA2." Nucleic Acids Research 48, no. 14 (2020): 7818–33. http://dx.doi.org/10.1093/nar/gkaa555.

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Abstract The tumor suppressor BRCA2 plays a key role in initiating homologous recombination by facilitating RAD51 filament formation on single-stranded DNA. The small acidic protein DSS1 is a crucial partner to BRCA2 in this process. In vitro and in cells (1,2), BRCA2 associates into oligomeric complexes besides also existing as monomers. A dimeric structure was further characterized by electron microscopic analysis (3), but the functional significance of the different BRCA2 assemblies remains to be determined. Here, we used biochemistry and electron microscopic imaging to demonstrate that the

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Scalise, Mariangela, Fabiola Marino, Luca Salerno, et al. "From Spheroids to Organoids: The Next Generation of Model Systems of Human Cardiac Regeneration in a Dish." International Journal of Molecular Sciences 22, no. 24 (2021): 13180. http://dx.doi.org/10.3390/ijms222413180.

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Organoids are tiny, self-organized, three-dimensional tissue cultures that are derived from the differentiation of stem cells. The growing interest in the use of organoids arises from their ability to mimic the biology and physiology of specific tissue structures in vitro. Organoids indeed represent promising systems for the in vitro modeling of tissue morphogenesis and organogenesis, regenerative medicine and tissue engineering, drug therapy testing, toxicology screening, and disease modeling. Although 2D cell cultures have been used for more than 50 years, even for their simplicity and low-c

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Silveira, Guilherme F., Pryscilla F. Wowk, Allan H. D. Cataneo, et al. "Human T Lymphocytes Are Permissive for Dengue Virus Replication." Journal of Virology 92, no. 10 (2018): e02181-17. http://dx.doi.org/10.1128/jvi.02181-17.

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ABSTRACTDengue virus (DV) infection can cause either a self-limiting flu-like disease or a threatening hemorrhage that may evolve to shock and death. A variety of cell types, such as dendritic cells, monocytes, and B cells, can be infected by DV. However, despite the role of T lymphocytes in the control of DV replication, there remains a paucity of information on possible DV-T cell interactions during the disease course. In the present study, we have demonstrated that primary human naive CD4+and CD8+T cells are permissive for DV infection. Importantly, both T cell subtypes support viral replic

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Deszcz, Luiza, Regina Cencic, Carla Sousa, Ernst Kuechler, and Tim Skern. "An Antiviral Peptide Inhibitor That Is Active against Picornavirus 2A Proteinases but Not Cellular Caspases." Journal of Virology 80, no. 19 (2006): 9619–27. http://dx.doi.org/10.1128/jvi.00612-06.

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ABSTRACT The replication of many viruses is absolutely dependent on proteolytic cleavage. Infected cells also use this biological mechanism to induce programmed cell death in response to viral infection. Specific inhibitors for both viral and cellular proteases are therefore of vital importance. We have recently shown that the general caspase inhibitor zVAD.fmk inhibits not only caspases, but also the 2A pro of human rhinoviruses (HRVs) (L. Deszcz, J. Seipelt, E. Vassilieva, A. Roetzer, and E. Kuechler, FEBS Lett. 560:51-55, 2004). Here, we describe a derivative of zVAD.fmk that inhibits HRV2

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Guo, Hui Shan, Juan José López-Moya, and Juan Antonio García. "Mitotic Stability of Infection-Induced Resistance to Plum Pox Potyvirus Associated with Transgene Silencing and DNA Methylation." Molecular Plant-Microbe Interactions® 12, no. 2 (1999): 103–11. http://dx.doi.org/10.1094/mpmi.1999.12.2.103.

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Plum pox potyvirus (PPV) infection of transgenic Nicotiana benthamiana plants that expressed the PPV NIb RNA replicase carrying a Gly to Val mutation at the GDD motif (NIbV lines) induced a phenotype of virus resistance and transgene silencing, which was not transmissible to the progeny after self-fertilization (H. S. Guo and J. A. García, Mol. Plant-Microbe Interact. 10:160-170, 1997). Here, we demonstrate that the induced resistance of NIbV plants is mitotically stable after plant propagation by grafting and by in vitro regeneration. Virus replication or residual virus RNA seem not to be req

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Eriksson, Jesper M., and Elisabeth Haggård-Ljungquist. "The Multifunctional Bacteriophage P2 Cox Protein Requires Oligomerization for Biological Activity." Journal of Bacteriology 182, no. 23 (2000): 6714–23. http://dx.doi.org/10.1128/jb.182.23.6714-6723.2000.

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ABSTRACT The Cox protein of bacteriophage P2 is a multifunctional protein of 91 amino acids. It is directly involved in the site-specific recombination event leading to excision of P2 DNA out of the host chromosome. In this context, it functions as an architectural protein in the formation of the excisome. Cox is also a transcriptional repressor of the P2 Pc promoter, thereby ensuring lytic growth. Finally it promotes derepression of prophage P4, a nonrelated defective satellite phage, by activating the P4 PLL promoter that controls P4 DNA replication. In this case it binds upstream of the PLL

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Díaz-Yáñez, Fernando, Ricardo Álvarez, Iván L. Calderón, Juan A. Fuentes, and Fernando Gil. "CdsH Contributes to the Replication of Salmonella Typhimurium inside Epithelial Cells in a Cysteine-Supplemented Medium." Microorganisms 8, no. 12 (2020): 2019. http://dx.doi.org/10.3390/microorganisms8122019.

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Salmonella Typhimurium is a facultative, intracellular pathogen whose products range from self-limited gastroenteritis to systemic diseases. Food ingestion increases biomolecules’ concentration in the intestinal lumen, including amino acids such as cysteine, which is toxic in a concentration-dependent manner. When cysteine’s intracellular concentration reaches toxic levels, S. Typhimurium expresses a cysteine-inducible enzyme (CdsH), which converts cysteine into pyruvate, sulfide, and ammonia. Despite this evidence, the biological context of cdsH’s role is not completely clear, especially in t

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Primadharsini, Putu Prathiwi, Shigeo Nagashima, Masaharu Takahashi, Kazumoto Murata, and Hiroaki Okamoto. "Ritonavir Blocks Hepatitis E Virus Internalization and Clears Hepatitis E Virus In Vitro with Ribavirin." Viruses 14, no. 11 (2022): 2440. http://dx.doi.org/10.3390/v14112440.

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Hepatitis E virus (HEV) is increasingly recognized as the leading cause of acute hepatitis. Although HEV infections are mostly self-limiting, a chronic course can develop especially in those with immunocompromised state. Ribavirin is currently used to treat such patients. According to various reports on chronic HEV infections, a sustained virological response (SVR) was achieved in approximately 80% of patients receiving ribavirin monotherapy. To increase the SVR rate, drug combination might be a viable strategy, which we attempted in the current study. Ritonavir was identified in our previous

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Jain, Mamta K., Mamta K. Jain, Hesham Sadek, et al. "525. Atovaquone for Treatment of COVID-19 (Ataq COVID-19) Trial." Open Forum Infectious Diseases 8, Supplement_1 (2021): S363—S364. http://dx.doi.org/10.1093/ofid/ofab466.724.

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Abstract Background Our group performed an in-silico screen to identify FDA approved drugs that inhibit SARS-C0V-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods Enrolled patients were randomized in a 2:1 fashion to atovaquone 1500 mg twice daily versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Patients agr

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Asgari, Samira, Luregn J. Schlapbach, Stéphanie Anchisi, et al. "Severe viral respiratory infections in children with IFIH1 loss-of-function mutations." Proceedings of the National Academy of Sciences 114, no. 31 (2017): 8342–47. http://dx.doi.org/10.1073/pnas.1704259114.

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Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome sequencing, we identified and characterized three rare loss-of-function variants in IFIH1, which encodes an RIG-I-like receptor involved in the sensing of viral RNA. Functional testing of the variants IFIH1 alleles demonstrated

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Liu, Nanxin, Zeyu Yang, Yuying Liu, et al. "Identification of a Putative SARS-CoV-2 Main Protease Inhibitor through In Silico Screening of Self-Designed Molecular Library." International Journal of Molecular Sciences 24, no. 14 (2023): 11390. http://dx.doi.org/10.3390/ijms241411390.

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There have been outbreaks of SARS-CoV-2 around the world for over three years, and its variants continue to evolve. This has become a major global health threat. The main protease (Mpro, also called 3CLpro) plays a key role in viral replication and proliferation, making it an attractive drug target. Here, we have identified a novel potential inhibitor of Mpro, by applying the virtual screening of hundreds of nilotinib-structure-like compounds that we designed and synthesized. The screened compounds were assessed using SP docking, XP docking, MM-GBSA analysis, IFD docking, MD simulation, ADME/T

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Oo, Adrian, Pouya Hassandarvish, Sek Peng Chin, Vannajan Sanghiran Lee, Sazaly Abu Bakar, and Keivan Zandi. "In silico study on anti-Chikungunya virus activity of hesperetin." PeerJ 4 (October 26, 2016): e2602. http://dx.doi.org/10.7717/peerj.2602.

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BackgroundThe re-emerging,Aedes spp.transmitted Chikungunya virus (CHIKV) has recently caused large outbreaks in a wide geographical distribution of the world including countries in Europe and America. Though fatalities associated with this self-remitting disease were rarely reported, quality of patients’ lives have been severely diminished by polyarthralgia recurrence. Neither effective antiviral treatment nor vaccines are available for CHIKV. Our previous in vitro screening showed that hesperetin, a bioflavonoid exhibits inhibitory effect on the virus intracellular replication. Here, we pres

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Gao, Yong, Michael A. Lobritz, Justin Roth, et al. "Targets of Small Interfering RNA Restriction during Human Immunodeficiency Virus Type 1 Replication." Journal of Virology 82, no. 6 (2008): 2938–51. http://dx.doi.org/10.1128/jvi.02126-07.

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ABSTRACT Small interfering RNAs (siRNAs) have been shown to effectively inhibit human immunodeficiency virus type 1 (HIV-1) replication in vitro. The mechanism(s) for this inhibition is poorly understood, as siRNAs may interact with multiple HIV-1 RNA species during different steps of the retroviral life cycle. To define susceptible HIV-1 RNA species, siRNAs were first designed to specifically inhibit two divergent primary HIV-1 isolates via env and gag gene targets. A self-inactivating lentiviral vector harboring these target sequences confirmed that siRNA cannot degrade incoming genomic RNA.

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