scholarly journals Genetic Determinants Responsible for Acquisition of Dengue Type 2 Virus Mouse Neurovirulence

1998 ◽  
Vol 72 (2) ◽  
pp. 1647-1651 ◽  
Author(s):  
Michael Bray ◽  
Ruhe Men ◽  
Issei Tokimatsu ◽  
Ching-Juh Lai
Keyword(s):  
Amino Acid ◽  
Serial Passage ◽  
Minor Effect ◽  
Genetic Determinants ◽  
Dengue Viruses ◽  
Ns1 Gene ◽  
Significant Attenuation ◽  
A Minor ◽  
Dengue Type 2 Virus

ABSTRACT Studies conducted some 50 years ago showed that serial intracerebral passage of dengue viruses in mice selected for neurovirulent mutants that also exhibited significant attenuation for humans. We investigated the genetic basis of mouse neurovirulence of dengue virus because it might be directly or indirectly associated with attenuation for humans. Analysis of the sequence in the C-PreM-E-NS1 region of the parental dengue type 2 virus (DEN2) New Guinea C (NGC) strain and its mouse-adapted, neurovirulent mutant revealed that 10 nucleotide changes occurred during serial passage in mice. Seven of these changes resulted in amino acid substitutions, i.e., Leu55-Phe and Arg57-Lys in PreM, Glu71-Asp, Glu126-Lys, Phe402-Ile, and Thr454-Ile in E, and Arg105-Gln in NS1. The sequence of C was fully conserved between the parental and mutant DEN2. We constructed intertypic chimeric dengue viruses that contained the PreM-E genes or only the NS1 gene of neurovirulent DEN2 NGC substituting for the corresponding genes of DEN4. The DEN2 (PreM-E)/DEN4 chimera was neurovirulent for mice, whereas DEN2 (NS1)/DEN4 was not. The mutations present in the neurovirulent DEN2 PreM-E genes were then substituted singly or in combination into the sequence of the nonneurovirulent, parental DEN2. Intracerebral titration of the various mutant chimeras so produced identified two amino acid changes, namely, Glu71-Asp and Glu126-Lys, in DEN2 E as being responsible for mouse neurovirulence. The conservative amino acid change of Glu71-Asp probably had a minor effect, if any. The Glu126-Lys substitution in DEN2 E, representing a change from a negatively charged amino acid to a positively charged amino acid, most likely plays an important role in conferring mouse neurovirulence.

scholarly journals Molecular Characterization and Evolutionary Analyses of Carnivore Protoparvovirus 1 NS1 Gene

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 308 ◽  
Author(s):  
Francesco Mira ◽  
Marta Canuti ◽  
Giuseppa Purpari ◽  
Vincenza Cannella ◽  
Santina Di Bella ◽  
...  
Keyword(s):  
Amino Acid ◽  
Negative Selection ◽  
Gene Sequence ◽  
Severe Disease ◽  
Divergent Evolution ◽  
Limited Information ◽  
Feline Panleukopenia Virus ◽  
Ns1 Gene ◽  
Canine Parvovirus Type 2

Carnivore protoparvovirus 1 is the etiological agent of a severe disease of terrestrial carnivores. This unique specie encompasses canine parvovirus type 2 (CPV-2) and feline panleukopenia virus (FPLV). Studies widely analyzed the main capsid protein (VP2), but limited information is available on the nonstructural genes (NS1/NS2). This paper analyzed the NS1 gene sequence of FPLV and CPV strains collected in Italy in 2009–2017, along with worldwide related sequences. Differently from VP2, only one NS1 amino-acid residue (248) clearly and constantly distinguished FPLV from CPV-2, while five possible convergent amino-acid changes were observed that may affect the functional domains of the NS1. Some synonymous mutation in NS1 were non-synonymous in NS2 and vice versa. No evidence for recombination between the two lineages was found, and the predominance of negative selection pressure on NS1 proteins was observed, with low and no overlap between the two lineages in negatively and positively selected codons, respectively. More sites were under selection in the CPV-2 lineage. NS1 phylogenetic analysis showed divergent evolution between FPLV and CPV, and strains were clustered mostly by country and year of detection. We highlight the importance of obtaining the NS1/NS2 coding sequence in molecular epidemiology investigations.

scholarly journals Substitution or deletion mutations between nt 54 and 70 in the 5′ non-coding region of dengue type 2 virus produce variable effects on virus viability

2007 ◽  
Vol 88 (6) ◽  
pp. 1748-1752 ◽  
Author(s):  
Wipawan Sirigulpanit ◽  
Richard M. Kinney ◽  
Vijittra Leardkamolkarn
Keyword(s):  
Infectious Clone ◽  
Single Point ◽  
Serial Passage ◽  
Coding Region ◽  
Deletion Mutations ◽  
Nucleotide Mutation ◽  
Virus Produce ◽  
Dengue Type 2 Virus ◽  
Stem Structure

A C57U nucleotide mutation in a predicted RNA stem structure (nt 11–16/56–61) of the 5′ non-coding region (5′NCR) of dengue 2 (DEN-2) 16681 virus is partially attenuating, but unstable during serial passage of certain candidate DEN-2 PDK-53-based vaccine viruses containing this mutation. Here, 11 different mutations (one or more point substitution and/or deletion) between nt 54 and 70 in the 5′NCR of the pD2/IC-30P-A (16681) infectious clone are described. Four mutants were infectious. Three mutants with single point substitutions replicated well in cell culture and exhibited variable neurovirulence in mice. Constructs containing multiple substitutions or any deletions failed to produce infectious viruses. Unexpectedly, a double C57U+G58C mutant replicated as efficiently as D2/IC-30P-A virus, and was more neurovirulent for newborn ICR mice. Thus, despite its predicted additional disruption of the RNA stem structure, the engineered contiguous secondary G58C mutation caused reversion of the partially attenuated phenotype caused by the 5′NCR-C57U mutation.

scholarly journals Polymorphisms of the PPAR-γ(rs1801282) and Its Coactivator (rs8192673) Have a Minor Effect on Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Aleš Pleskovič ◽  
Marija Šantl Letonja ◽  
Andreja Cokan Vujkovac ◽  
Jovana Nikolajević Starćević ◽  
Danijel Petrovič
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Coronary Atherosclerosis ◽  
Carotid Atherosclerosis ◽  
Minor Effect ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
A Minor

Background. The present study was designed to clarify whether common single nucleotide polymorphisms (SNPs) of the Peroxisome Proliferator-Activated Receptor-γ(PPAR-γ) gene (rs1801282) and the Peroxisome Proliferator-Activated Receptor-γCoactivator-1 (PGC-1α) gene (rs8192673) are associated with markers of carotid and coronary atherosclerosis in Caucasians with type 2 diabetes mellitus (T2DM).Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled in the cross-sectional study. Markers of carotid atherosclerosis were assessed ultrasonographically. In 215 out of 595 subjects with T2DM, a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of either rs1801282 or rs8192673 was performed using KASPar assays.Results. In our study, we demonstrated an effect of the rs1801282 on markers of carotid atherosclerosis (presence of plaques) in Caucasians with T2DM in univariate and in multivariable linear regression analyses. Finally, we did not demonstrate any association between either rs1801282 or rs8192673 and markers of coronary atherosclerosis.Conclusions. In our study, we demonstrated a minor effect of the rs1801282 on markers of carotid atherosclerosis (presence of plaques) in Caucasians with T2DM. Moreover, we demonstrated a minor effect of the rs8192673 on CIMT progression in the 3.8-year follow-up in Caucasians with T2DM.

301-LB: Effects of Amino Acid Restriction on Development of Type 2 Diabetes in NZO Mice by FGF21 Secretion

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 301-LB
Author(s):  
TERESA CASTAÑO-MARTINEZ ◽  
WENKE JONAS ◽  
DANIELA WEBER ◽  
CORNELIA WEIKERT ◽  
THOMAS LAEGER
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acid ◽  
Nzo Mice

Improvement of monitoring of tertiary filtration with particle counting

2006 ◽  
Vol 6 (1) ◽  
pp. 1-9
Author(s):  
V. Miska ◽  
J.H.J.M. van der Graaf ◽  
J. de Koning
Keyword(s):  
Particle Surface ◽  
Minor Effect ◽  
Particle Size Distributions ◽  
Particle Volume ◽  
Mass Distributions ◽  
Particle Counting ◽  
Total Particle ◽  
Particle Counts ◽  
A Minor ◽  
Sample Dilution

Nowadays filtration processes are still monitored with conventional analyses like turbidity measurements and, in case of flocculation–filtration, with phosphorus analyses. Turbidity measurements have the disadvantage that breakthrough of small flocs cannot be displayed, because of the blindness regarding changes in the mass distributions. Additional particle volume distributions calculated from particle size distributions (PSDs) would provide a better assessment of filtration performance. Lab-scale experiments have been executed on a flocculation–filtration column fed with effluent from WWTP Beverwijk in The Netherlands. Besides particle counting at various sampling points, the effect of sample dilution on the accuracy of PSD measurements has been reflected. It was found that the dilution has a minor effect on PSD of low turbidity samples such as process filtrate. The correlation between total particle counts, total particle volume (TPV) and total particle surface is not high but is at least better for diluted measurements of particles in the range 2–10 μm. Furthermore, possible relations between floc-bound phosphorus and TPV removal had been investigated. A good correlation coefficient is found for TPV removal versus floc-bound phosphorus removal for the experiments with polyaluminiumchloride and the experiments with single denitrifying and blank filtration.

scholarly journals Linkage mapping identifies a non-synonymous mutation in FLOWERING LOCUS T (FT-B1) increasing spikelet number per spike

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonathan Brassac ◽  
Quddoos H. Muqaddasi ◽  
Jörg Plieske ◽  
Martin W. Ganal ◽  
Marion S. Röder
Keyword(s):  
Flowering Time ◽  
Aspartic Acid ◽  
Synonymous Substitution ◽  
Minor Effect ◽  
Phenotypic Variance ◽  
Spikelet Number ◽  
Wheat Varieties ◽  
Trait Locus ◽  
A Minor ◽  
Spikelet Number Per Spike

AbstractTotal spikelet number per spike (TSN) is a major component of spike architecture in wheat (Triticumaestivum L.). A major and consistent quantitative trait locus (QTL) was discovered for TSN in a doubled haploid spring wheat population grown in the field over 4 years. The QTL on chromosome 7B explained up to 20.5% of phenotypic variance. In its physical interval (7B: 6.37–21.67 Mb), the gene FLOWERINGLOCUST (FT-B1) emerged as candidate for the observed effect. In one of the parental lines, FT-B1 carried a non-synonymous substitution on position 19 of the coding sequence. This mutation modifying an aspartic acid (D) into a histidine (H) occurred in a highly conserved position. The mutation was observed with a frequency of ca. 68% in a set of 135 hexaploid wheat varieties and landraces, while it was not found in other plant species. FT-B1 only showed a minor effect on heading and flowering time (FT) which were dominated by a major QTL on chromosome 5A caused by segregation of the vernalization gene VRN-A1. Individuals carrying the FT-B1 allele with amino acid histidine had, on average, a higher number of spikelets (15.1) than individuals with the aspartic acid allele (14.3) independent of their VRN-A1 allele. We show that the effect of TSN is not mainly related to flowering time; however, the duration of pre-anthesis phases may play a major role.

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