Synthesis and molecular docking of N′-arylidene-5-(4-chlorophenyl)-1-(3,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbohydrazides as novel hypoglycemic and antioxidant dual agents

Herein, the design and synthesis of 10 novel N′-arylidene pyrazole-3-carbohydrazides are described. Compounds were pretended to act as dual agents against diabetes and oxidative stress, two correlated pathologies involved in metabolic syndrome development and progression. The antioxidant capacity was evaluated by means of DPPH and FRAP in vitro assays. It was found that compounds bearing a hydroxyl group at 4-position of the hydrazone moiety are potent antioxidant entities, being compound 3g (a syringaldehyde derivative) the most active compound. In addition, the in vivo hypoglycemic effect of the analogues was determined. With regard to the above, the cinnamaldehyde derivatives showed a scarce biological activity, while the 4-hydroxy analogues showed the higher glycemia reduction at 7 h after administration. Interestingly, the most potent antioxidants 3b and 3g also were of the most active compounds in reducing the plasma glucose, reaching 80% of reduction in the case of 3g. Molecular docking binding poses conducted to a plausible interpretation of the biological outcomes and a possible interaction between a hydroxy group and Asn287 of CB1R was proposed as an important feature for enhancing the observed activity.     

An immunochemical method for the detection of the expression of human gene loci in human-rodent somatic cell hybrids with special reference to the GPI locus

Species-specific antibodies, prepared against unpurified human and Chinese hamster fibroblast extracts, were used to identify the parental origins of enzymes in human-hamster somatic cell hybrids. Results of the detection of the expression of the human glucosephosphate isomerase gene locus (GPI) by electrophoretic and immunochemical techniques were concordant in 17 instances. The human GPI synthesized by fibroblasts derived from skin explants and by somatic cell hybrids retaining the human GPI locus, regardless of whether the human parental cells were lymphocytes or fibroblasts, appeared to be antigenically identical.This work was supported by the Medical Research Council of Canada (Grant MA-4061). Personnel and operating support were provided by The Children's Hospital of Winnipeg Research Foundation, Inc.     

Chromosomal inheritance patterns of intergeneric hybrids of ictalurid catfishes: odd diploid numbers with equal parental contributions

Hybrid chromosomal compositions of channel catfish Ictalurus punctatus × black bullhead Ameiurus melas and channel catfish × flathead catfish Pylodictis olivaris were analysed by a computer-based method. The karyotype of each hybrid was highly asymmetric, and the diploid numbers and arm numbers were intermediate to the parental types. The hybrid offspring of channel catfish × black bullhead possessed a diploid number of 59 chromosomes, with an arm number estimate of 87. The hybrid offspring of the channel catfish × flathead catfish cross possessed a diploid number of 57 chromosomes, also with an arm number estimate of 87. Nucleolus organizer regions (NORs) were located on a single pair of chromosomes with symmetric staining intensity in channel catfish and in black bullhead, and on a single pair of chromosomes with asymmetric staining intensity in flathead catfish. The channel catfish × black bullhead hybrid had two unpaired chromosomes that stained positively for NORs. The channel catfish × flathead catfish had three unpaired chromosomes that stained positively for NORs. Specific marker chromosomes were identified in each hybrid. There was no evidence of androgenesis, gynogenesis, polyploidy or aneuploidy in the hybrids. Results of this study, plus information reported previously, indicate that chromosomes of ictalurid catfishes are inherited stably in a haploid pattern with an equal contribution to the genomes of F₁ hybrids, even in intergeneric crosses involving divergent numbers of parental chromosomes.     

Modification of the lead molecule: Tryptophan and piperidine appended triazines reversing inflammation and hyeperalgesia in rats

The structural optimization of the molecules making them to fit into the active site pocket of COX-2 occupying the same space as covered by the natural substrate arachidonic acid helped in the emergence of compound 10 as an efficacious anti-inflammatory agent. Selective for COX-2 over COX-1, compound 10 exhibited IC₅₀ 0.02 µM for COX-2 and reversed acetic acid induced inflammation in rats by 73% when used at 10 mg kg⁻¹ dose and the same dose of the compound also rescued the animals from inflammatory phase of formalin induced hyperalgesia. As evidenced by the results of molecular modeling studies supported by the nuclear Overhauser enhancement data, the appropriate geometry of the molecule in the active site pocket of COX-2 contributing to its H-bond/hydrophobic interactions with Ser530, Trp387 and Tyr385 seems responsible for the enzyme inhibitory activity of the compound.     

TERRA and RAD51AP1 promote alternative lengthening of telomeres through an R- to D-loop switch

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Production and cytogenetics of hybrids of Triticum aestivum x Leymus innovatus

Summary Hybrid plants were obtained between Triticum aestivum (2n=6x=42, AABBDD) and Leymus innovatus (2n=4x=28, JJNN) at a frequency varying from 0.4% to 1.2% of the pollinated florets. Improvement of the embryo culture medium resulted in a higher frequency of embryo rescue. Eight of ten hybrids had the expected chromosome number of 35 (ABDJN). Meiotic analysis indicated that there was no homology between the genomes of the two species. Two hybrids had only 28 chromosomes. Comparison of chromosome pairing between the two types of hybrids suggested that Leymus innovatus carries genes that affect chromosome pairing and behavior. The relatively high occurrence of spontaneous doubling in the meiocytes of these hybrids may indicate that backcrossing of the hybrids to wheat should be possible, although frequent chromosome irregularities observed in the meiocytes of the hybrids may decrease the probability of success of this step, which is essential to the process of gene transfer from L. innovatus to wheat.Contrib. no. 366     

Chloroplast DNA assorts randomly in intraspecific somatic hybrids of Nicotiana debneyi

Summary Plants were regenerated following intraspecific fusion of leaf protoplasts from two naturally occurring genotypes of Nicotiana debneyi. The two genotypes differed in the EcoRl fragmentation pattern of chloroplast DNA and in the nuclear-coded phosphoglucomutase (Pgm) isozymes. There was no conscious selection for hybrid genotypes during protoplast culture or plant regeneration. Among 225 plants screened for Pgm, six were identified as nuclear hybrids. Restriction endonuclease and filter hybridisation analysis revealed that the cytoplasms of the hybrids contained one or other but never both parental chloroplast DNAs. The sorting out of chloroplasts was random and complete; the limit of detecting a rare chloroplast-DNA type in a mixture was 0.1%.     

Genetic variability in Plantago species in relation to their ecology

Summary Twelve Plantago major plants, good representatives of their populations, appeared to be genetically different for several characters which are important for adaptation to the respective habitat conditions. These characters are: juvenile growth, leaf morphology, production of secondary rosettes, flowering time, seed production, seed size and adult leaf production. The adaptive value of some of these characters was investigated by transplantation experiments in the field and by intraspecific competition experiments. The roadside type of ssp. major was adapted to trampling by being erect and elastic. The lawn type of ssp. major was adapted to a short, frequently cut, vegetation by being prostrate and by producing leaves with short petioles throughout the growth season. In the natural situations in which ssp. pleiosperma occurs, growth rate and first-year seed production of this subspecies were considerably higher than that of ssp. major. In a number of experiments, F₁s and F₂s were included, derived from crosses between the original plants. The F₁s were generally rather well adapted to both parental habitats, whereas the F₂s appeared to be less fit. The various alternatives in spending resources relevant for fitness optimization in different habitats are discussed.Grassland Species Research Group Publication No. 93     

Genetic Regulation of Liver Microsomal CYP2E1 Activity among Strains of the Viviparous Fishes Poeciliopsis occidentalis and Poeciliopsis lucida

The use of CYP2E1 (cytochrome P4502E1) expression as a biomarker for xenobiotic contamination may be useful, but for full understanding of the response, components of inheritance need to be understood. CYP2E1 expression was examined in P. lucida (M61-31), two strains of P. occidentalis (V87-15 and AV76-7), and their F1, F2, and backcross progeny. Phenotypic expression of CYP2E1 in Poeciliopsis has two distinct components – maximal activity and temperature optimum (T0) (Kaplan et al. 1991). In all P. occidentalis and P. lucida crosses, CYP2E1 activity segregated in up to three phenotypic groups. In F1 individuals (P. lucida×P. occidentalis V87-15), an overdominant phenotype was generated in 50% of the progeny. The P. lucida phenotype was absent suggesting a maternal effect on the F1 phenotype. Backcrosses of these F1 progeny to P. lucida females resulted in a recovery of the P. lucida phenotype while maintaining expression of an overdominant phenotype in 50% of the progeny. Among F2 progeny, an overdominant phenotype was expressed less often as compared to the F1 generation, and parental phenotypes were observed in equal numbers. Phenotypic expression patterns of CYP2E1 activity among F1 fish changed significantly with replacement of P. occidentalis V87-15 by P. occidentalis AV76-7. The P. lucida and P. occidentalis phenotype was equally distributed among progeny without evidence of an overdominant phenotype. Backcrosses of F1 progeny to P. lucida females resulted in equal amounts of the parental phenotypes. Backcross of an F1 male to a P. occidentalis AV76-7 female increased the P. occidentalis phenotype at the expense of the P. lucida phenotype in resulting progeny. Backcross of a F1 female to a P. lucida male resulted in equal distribution of the parental phenotypes. In addition, a greater number of F2 fish expressed the P. occidentalis phenotype as compared to the P. lucida phenotype. No significant difference in the sex ratios was seen in any of the crosses with the exception of one backcross.     

Mitochondrial DNA cytochrome b gene variation reveals different largemouth bass genealogies

A mitochondrial DNA character set based on cytochrome b gene variations is described that may be used in conjunction with established nuclear gene differences to assess largemouth bass Micropterus salmoides population structure and dynamics. Alignment of known cytochrome b sequences revealed two regions where the functional constraints of the molecule appear to be sufficiently reduced to allow several amino acid substitutions. Restriction analysis was used to probe nucleotide variation within one of these evolutionary hotspots, resulting in the discovery of fixed largemouth bass subspecific cytochrome b haplotypes. Application of two molecular character sets, one founded on fixed allelic variation in nuclear genes and the other on mtDNA cytochrome b diversity, revealed that in several Texas populations, where the Florida subspecies was introduced into extant populations of northern largemouth bass, hybridization was evident. The direction of the introgression vector could be determined through the combination of both character Sets.