The position of the epistatic S locus in the halothane linkage group in pigs

The linkage of the Phi, Pgd, Po2, S, H and halothane sensitivity loci was followed in a Belgian Landrace family, heterozygous for these systems over 6 generations. Recombination next to the S locus occurred mainly in pigs belonging to this particular family. From this investigation the position of the S locus is proved to be outwith the Phi-Pgd region, next to Phi . Therefore the gene sequence S - Phi - Hal -H- Po2 -Pgd is proposed. Higher recombination rates were observed in the female parental line of the multiheterozygous family when compared to the male parental line. Additional data from animals, unrelated to this strain, confirm the evidence of close linkage of the S system to the nearest marker loci.     

Prediction of the halothane (Hal) genotypes of pigs by deducing Hal, Phi, Po2, Pgd haplotypes of parents and offspring: results from a large-scale practice in Swedish breeds

Results from a large-scale study, comprising 75 different breeding herds, are reported on predicting the halothane ( Hal ) genotypes of individual pigs by making use of the known close linkage between Hal and three C blood marker loci ( Phi, Po2, Pgd ). The parents haplotypes (involving Hal and marker loci) were determined from the HAL phenotypes (halothane test results) and marker loci phenotypes of their offspring in the first one or two litters studied. In subsequent litters of the Hal -marker loci haplotyped parents, the offspring's expected Hal genotypes could be predicted on the basis of the marker loci haplotypes inherited by them. By comparing the expected and observed HAL phenotypes of offspring in subsequent litters, the predicted Hal genotype was found to be correct in 90–95 % of the 4000 offspring (from Nn × Nn and Nn × nn matings) of Swedish Landrace and Yorkshire breeds studied.
The order of the three marker loci was confirmed as Phi-Po2-Pgd but the position of Hal with regards to Phi could not be resolved. The recombination frequencies between the most distant loci in this region, viz. Hal-Pgd and Phi-Pgd , were estimated to be 3–4.5 % and 4–6 % , respectively. The easy and rapid electrophoretic techniques described in the study to phenotype PHI, PO2, PGD, also allowed phe-notyping of six other polymorphic protein systems on the same gels. Thus Hal genotyping and effective parentage control can be conducted simultaneously.     

Multiple mating and sperm displacement in a natural population of Drosophila melanogaster

Summary Mother-offspring data for alcohol dehydrogenase genotypes of a vineyard cellar population of D. melanogaster are best explained by a model that allows 21% of females in the population to mate twice with an 83% level of sperm displacement. A population model with multiple mating and sperm displacement is examined theoretically. A formula for the effective population size is derived under this model. Multiple mating increases the effective population size relative to single mating.     

A single succinic semialdehyde dehydrogenase is involved in 4-hydroxyphenylacetate and 4-aminobutyrate catabolism in Klebsiella pneumoniae M5a1

Abstract Klebsiella pneumoniae M5a1 grows readily on two compounds, 4-hydroxyphenylacetate and 4-aminobutyrate, whose catabolism produces succinic semialdehyde. A single succinic semialdehyde dehydrogenase was detected, native molecular weight 52000, that has NAD as the preferred cofactor and is induced by succinic semialdehyde functions in the oxidation of succinic semialdehyde during growth on both 4-hydroxyphenyl-acetate and 4-aminobutyrate. This contrasts with the situation for Escherichia coli and Pseudomonas putida where two distinct forms of succinic semialdehyde dehydrogenase have been observed.     

Effect of carbamate herbicides on VA mycorrhizal infection and plant growth

Summary The effect of the carbamate herbicides Chlorpropham, Sulfallate and Phenmedipham, which are believed to inhibit photosynthesis, on VA mycorrhizal infection and on plant growth, were examined. Foliar spraying of Phenmedipham decreased the root concentration of total and reducing sugars and the fungal metabolism (using a staining reaction for succinate dehydrogenase as indicator) 48 h after application. However, all three carbamate herbicides tested, whether applied by foliar spray or directly to soil, did not affect the amount of VA mycorrhizal infection present at the end of the experiment. These herbicides decreased plant growth when they were applied to soil. But when the herbicides were sprayed only Phenmedipham, applied at high concentrations, decreased plant growth. Moreover, our results show that VA mycorrhizas may help plants recover from the deleterious effect of Phenmedipham.     

The formation of L-3-phosphoglyceric acid by ribulose-1,5-bisphosphate carboxylase

A sensitive and reliable method to determine the stereochemical composition of 3-phosphoglyceric acid is presented. Results obtained with this method show that 3-phosphoglyceric acid formed in the ribulose-1,5-bisphosphate carboxylase reaction is a mixture of 10% L-3-PGA and 90% D-3-PGA.     

Ultrastructural changes in isolated rat hepatocytes exposed to different CCl4 concentrations

Ultrastructural data are presented on time-course changes in isolated rat hepatocyte suspensions exposed either to 1.2 or 1.8 mM CCl4 for up to 1 h. The subcellular changes at the lower concentration, but not the higher, are shown to closely parallel those reported to occur in rat hepatocytes following ingestion of CCl4.     

Alcohol dehydrogenase isozymes in the mouse: Genetic regulation, allelic variation among inbred strains and sex differences of liver and kidney A2 isozyme activity

Genetic analysis of a proposed cis-acting temporal locus ( Adh-3t ), which regulates alcohol dehydrogenase C₂ (ADH-C₂) acitivity in mouse epididymis extracts, among F₁ (ddN × BALB/c) × ddN male backcross progeny provided evidence for genetic distinctness between the structural ( Adh-3 ) and temporal ( Adh-3t ) loci on chromosome 3. Genetic analysis also confirmed the close, linkage of Adh-1 (encoding liver and kidney ADH-A₂) and Adh-3 (encoding stomach ADH-C₂) to within 0.3 centimorgans on the mouse genome. Evidence is presented for a proposed closely linked cis-acting temporal locus (designated Adh-1t ) for the A₂ isozyme (encoded by Adh-1 ) controlling the activity of this enzyme in mouse kidney extracts, but having no apparent affect on liver and intestine ADH-A₂ activities. An extensive survey of the distribution of Adh-1, Adh-3 and Adh-3t alleles among 65 strains of mice is reported — with the exception of two Japanese strains (ddN and KF), linkage disequilibrium between Adh-3 and Adh-3t was observed. Sex differences in mouse liver and kidney ADH-A₂ activities were observed, with male/female ratios of approximately 0.6 and 3 respectively for these tissue extracts.     

DIA-Based Proteomics Identifies IDH2 as a Targetable Regulator of Acquired Drug Resistance in Chronic Myeloid Leukemia

Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR.