Aryl uracil inhibitors of hepatitis C virus NS5B polymerase: Synthesis and characterization of analogs with a fused 5,6-bicyclic ring motif

The synthesis and structure–activity relationships of a novel aryl uracil series which contains a fused 5,6-bicyclic ring unit for HCV NS5B inhibition is described. Several analogs display replicon cell culture potencies in the low nanomolar range along with excellent rat pharmacokinetic values.     

Haplotype diversity of preharvest sprouting QTLs in wheat.

Preharvest sprouting (PHS) is one of the most important factors affecting wheat production worldwide in environments characterized by rainfall and high humidity at harvest. In such environments, the incorporation of seed dormancy of a limited duration is required to minimize losses associated with PHS. A global collection of 28 PHS-resistant and -susceptible wheat germplasm was characterized with microsatellite markers flanking the genomic regions associated with PHS-resistance quantitative trait loci (QTLs), particularly on chromosomes 3D and 4A. The genetic diversity analysis revealed 380 alleles at 54 microsatellite loci, with an average of 7.0 alleles per locus, among the 28 wheat genotypes. Gower's genetic similarity values among all possible pairs of genotypes varied from 0.44 to 0.97, indicating that there is considerable diversity in the PHS germplasm evaluated. Cluster and principal coordinates analysis of genetic similarity estimates differentiated the genotypes into groups, according to their source of PHS resistance. Three major SSR haplotypes were observed on chromosome 4AL, designated RL4137-type allele, Aus1408-type allele, and synthetic-hexaploid-type allele. The RL4137-type allele was prevalent in Canadian cultivars, mostly in cluster 6, followed by the Aus1408-type and its derivatives in clusters 4 and 5. The Syn36 and Syn37 alleles on chromosome 4AL were rare. On chromosome 3DL, the SSRs haplotypes derived from Syn36 and Syn37 were also rare, and proved unique to the Aegilops tauschii - derived synthetic hexaploids. They are therefore likely carrying resistance genes different from those previously reported. Based on genetic relationships, PHS resistance might be improved by selecting parental genotypes from different clusters.     

Haematological and serum biochemical reference values of snow trout,Schizothorax labiatus habiting in river Sindh of Indian Himalayan region

Haematological and serum biochemical parameters are a valuable tool in determining the wellbeing status of different fish species and response in close association to various biological and environmental factors, therefore the aim of the present study was to establish sex-wise reference values of haemato-biochemical parameters of S. labiatus. The haematological parameters such as haemoglobin (Hb) concentration, total erythrocyte count (RBC), total leucocyte count (WBC), packed cell volume (PCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV) and serum biochemical parameters such as glucose, cholesterol, urea, total protein, albumin and globulin were analysed. The results revealed that the haematological parameters, i.e., Hb, RBC, WBC and PCV showed significant (P < 0.05) differences with respect to sex. Significantly (P < 0.05) higher values of Hb content (11.18 g dl⁻¹), RBC count (1.88 × 10⁶ mm⁻³) and PCV (36.15%) were noted in male fish than females throughout the study period, while significantly (P < 0.05) higher WBC count was noted in females (20.38 × 10³ mm⁻³) compared to males. However, no significant (P > 0.05) difference was observed in erythrocyte indices like MCH, MCHC and MCV between sexes. The serum biochemical parameters, i.e., glucose, cholesterol and urea, also showed significant (P < 0.05) difference between the sexes, but no significant (P > 0.05) difference was noticed in total protein, albumin and globulin. Significantly (P < 0.05) highest values of glucose (116.76 mg dl⁻¹) and urea (9.01 mg dl⁻¹) were recorded in male S. labiatus, while highest value of cholesterol (223.53 mg dl⁻¹) was noted in females. The information generated in the present study gives the basic reference values of haematological and serum biochemical parameters of S. labiatus which will be useful in monitoring the wellbeing status of fish populations. Moreover, the data will also be helpful to ascertain the occurrence of different clinical and subclinical diseases, which may in turn help to boost the overall production of this species.     

Effect of low doses of the hydra peptide morphogen on protein biosynthesis in the intact and regenerating rat liver

The dependence of ornithine decarboxylase (ODC) activity on hydra peptide morphogen doses has been established. The parameters of protein synthesis were determined in normal and regenerating rat liver, using the peptide in a dose of 20 micrograms/kg body weight, initiating maximum enzyme activity. It was established that intraperitoneal injection of the peptide in partially hepatectomized animals stimulated ODS activity in dose-dependent manner and was dome-shaped. The peptide injection in intact animals does not affect the intensity of 3H-leucine inclusion into the liver protein and the protein content in rat liver. However, the peptide injection in partially hepatectomized animals increased the level of 3H-leucine inclusion into the protein of regenerating liver and stimulated protein accumulation in this type of tissue.     

Cloning and sequence analysis of the flagellin gene ofCampylobacter jejuni TGH9011

Flagella are essential for motility and have been implicated to be one of the pathogenic determinants. The flagellum ofCampylobacter jejuni is a polymeric structure of a 62-kd protein. Using a high-affinity flagellin antibody to screen a lambda gt 11 phage genomic expression library ofC. jejuni strain TGH9011 (Serotype LIO36), a recombinant phage clone lambda gt 11RK that expresses theC. jejuni flagellin protein was isolated. The recombinant lambda gt 11 RK produced a 56-kd protein upon induction with isopropylthiogalactoside, which reacted specifically with anti-flagellin antibody. The flagellin gene was sequenced, and comparative analysis of the nucleotide and amino acid sequence identified a region of the flagellin that shows hypervariability among differentCampylobacter species and strains.     

Approaches to laser speckle reduction for uniform illumination of the field of view of a microscope during biophysical studies

Biophysics - A comparative study of various approaches to speckle reduction showed that the use of a liquid crystal-based speckle reducer did not allow complete elimination of speckles. The use of...