The "Goldilocks Effect" in Cystic Fibrosis: identification of a lung phenotype in the <Emphasis Type="Italic">cftr</Emphasis> knockout and heterozygous mouse

Background  

Cystic Fibrosis is a pleiotropic disease in humans with primary morbidity and mortality associated with a lung disease phenotype. However, knockout in the mouse of cftr, the gene whose mutant alleles are responsible for cystic fibrosis, has previously failed to produce a readily, quantifiable lung phenotype.     

Structural Features of Pregna-D′-pentaranes Determining Their Interaction with Three Rat Proteins

Competition of a number of progesterone 16,17-cycloalkane derivatives with ³H-labeled ligands for the binding sites of rat uterine progesterone receptor, uterine pentaranophilin, and blood serum pentaranophilin was studied. We found that the selective ligands for the progesterone receptor are progesterone, 16,17-cyclopropanoprogesterone, and 16,17-cyclopent-3-enoprogesterone and the selective ligands for serum pentaranophilin are 6-methyl-16,17-cyclohexanopregna-1,4-diene-3,20-dione and 3-hydroxy-16,17-cyclohexanopregn-5-en-20-one. No selective ligands for the uterine pentaranophilin were found. The majority of substituents in rings A, B, and D we studied decreased the affinity of ligands for all the three proteins. The substitution of the ⁵-3-hydroxy grouping for the ⁴-3-keto grouping exerted the strongest negative effect in the case of the progesterone receptor and the uterine pentaranophilin, whereas the introduction of the 3,4-dimethyl grouping strongly inhibited the ligand affinity for the uterine pentaranophilin. The extent and even the direction of the effect of a substituent on the affinity of ligands for the proteins substantially depended on the presence of other substituents in the steroid molecules. We hypothesized that a certain similarity exists between three proteins studied in respect to the structures of their ligand-binding pockets.     

Genetic analysis of inheritance of mei8, sy1 and sy10 mutations,disrupting the correct meiosis in the rye Secale cereale L

It is shown that mutations mei8 (irregular condensation and fragmentation of meiotic chromosomes), sy1 (asynapsis), and sy10 (heterologous synapsis) of rye Secale cereal are nonallelic. In double mutants mei8 sy1 and mei8 sy10 both mutations are expressed simultaneously and independently of each other. A study of joint inheritance of mutations sy1 and sy10 revealed their interaction by means of recessive epistasis: the double mutants has the sy10 phenotype. This means that the sy10 gene controls an earlier stage of synapsis in meiotic prophase than the sy1 gene. Mutation mei8 is inherited independently of sy1 but it is linked to sy10 (recombination frequency 26.8 +/- 3.58%).     

The study of joint inheritance of mutations impairing the structure of meiotic chromosomes in rye Secale cereale L

Genetic analysis has demonstrated that meiotic mutations mei8 (irregular condensation and fragmentation of meiotic chromosomes) and mei10 (chromosome overcompaction) are nonallelic. Mutation mei10 exhibits digenic inheritance (with a segregation ratio of 13:3) in the combinations of crosses studied. It is assumed that the phenotypic expression of mutation mei10 is suppressed by the effect of recessive gene lch1 or lch2 (long chromosomes), both of which have been revealed in one of the parental lines (Mc10). These genes determine weak condensation of meiotic chromosomes. In double mutants mei8 mei10, the mutations are expressed independently of each other. Gene mei10 is linked with gene mei8 (r = 36.8 +/- 5.38%); genes lch1 and lch2 are not linked either with them or with each other. Taking into account the data on the linkage between genes mei10 and sy10 and between mei8 and sy10, the order of genes in the linkage group is shown to the following: mei8-sy10-mei10.     

Localization of cohesin complexes of polytene chromosomes of Drosophila melanogaster located on interbands

The distribution of cohesin complex in polytene chromosomes of Drosophila melanogaster was studied. Cohesin is a complicated protein complex which is regulated by the DRAD21 subunit. Using immunostaining for DRAD21p, the cohesins were shown to be preferentially located in the interband regions. This specificity was not characteristic for puffs, where uniform staining was observed. The presence of a few brightly fluorescent regions (five to ten per chromosome arm) enriched with cohesin complexes was shown. Some of these regions had permanent location, and the others, variable location. No antibody binding was detected in the chromocenter. Immunostaining of interphase nuclei of neuroblasts revealed large cohesin formations. On the polytene chromosomes of D. melanogaster, the Drad21 gene was mapped to the chromocentric region (81) of the L arm of chromosome 3.     

Itt1p, a novel protein inhibiting translation termination in Saccharomyces cerevisiae

Background

Termination of translation in eukaryotes is controlled by two interacting polypeptide chain release factors, eRFl and eRF3. eRFl recognizes nonsense codons UAA, UAG and UGA, while eRF3 stimulates polypeptide release from the ribosome in a GTP- and eRFl – dependent manner. Recent studies has shown that proteins interacting with these release factors can modulate the efficiency of nonsense codon readthrough.

Results

We have isolated a nonessential yeast gene, which causes suppression of nonsense mutations, being in a multicopy state. This gene encodes a protein designated Itt1p, possessing a zinc finger domain characteristic of the TRIAD proteins of higher eukaryotes. Overexpression of Itt1p decreases the efficiency of translation termination, resulting in the readthrough of all three types of nonsense codons. Itt1p interacts in vitro with both eRFl and eRF3. Overexpression of eRFl, but not of eRF3, abolishes the nonsense suppressor effect of overexpressed Itt1p.

Conclusions

The data obtained demonstrate that Itt1p can modulate the efficiency of translation termination in yeast. This protein possesses a zinc finger domain characteristic of the TRIAD proteins of higher eukaryotes, and this is a first observation of such protein being involved in translation.     

Effect of bacterial infection on the lipid composition of carp blood lymphocytes

The initial stage of bacterial infection is characterized by an increase in the level of total lipids and polyenoic fatty acids in membrane phospholipids of blood lymphocytes of carp (Cyprinus carpio L.). In the fish infected with aeromonads, changes in the ratios of fatty acids in phospholipids are similar for either lymphocytes, liver, or whole blood. The extent to which these changes are pronounced depends on the original physiological status of the fish.     

Stability of microbial association in the process of industrial biofiltration cleaning of gaseous discharges

Results of industrial exploitation of a biofiltration plant tailored for purifying gaseous discharges of hazardous organic components such as toluene, cyclohexane, and xylene, are examined. Both numerical and compositional variations were monitored for a long-term (more than 1.5 years) utilization process in an association of microorganisms decomposing organic pollutants. A population of microbial association composed by one yeast and two bacterial strains in the biofilm on the surface of filtering sheets was abundant (10(8)-10(9) yeast cells/cm2 and 10(10)-10(11) bacterial cells/cm2) and stable during the whole period of monitoring. A microbial association in the culture medium averaging 10(6) yeast cells/l and 10(8) bacterial cells/l is more susceptible to technogenic impacts and seasonal fluctuations. Overall, the biofilter as an open and autonomic system maintained its microbial association, thereby providing a high-degree (93-98%) purification of industrial gaseous discharges from organic pollutants.