Selection against genetic defects in conservation schemes while controlling inbreeding

We studied different genetic models and evaluation systems to select against a genetic disease with additive, recessive or polygenic inheritance in genetic conservation schemes. When using optimum contribution selection with a restriction on the rate of inbreeding (ΔF) to select against a disease allele, selection directly on DNA-genotypes is, as expected, the most efficient strategy. Selection for BLUP or segregation analysis breeding value estimates both need 1–2 generations more to halve the frequency of the disease allele, while these methods do not require knowledge of the disease mutation at the DNA level. BLUP and segregation analysis methods were equally efficient when selecting against a disease with single gene or complex polygene inheritance, i.e. knowledge about the mode of inheritance of the disease was not needed for efficient selection against the disease. Smaller schemes or schemes with a more stringent restriction on ΔF needed more generations to halve the frequency of the disease alleles or the fraction of diseased animals. Optimum contribution selection maintained ΔF at its predefined level, even when selection of females was at random. It is argued that in the investigated small conservation schemes with selection against a genetic defect, control of ΔF is very important.     

Leishmania donovani: structural insignt in the recognition of C-methylated analogues of spermidine as natural polyamine

The ability of alpha-, beta-, gamma- and omega-methylated spermidine analogues to restore the growth of L. donovani promastigotes that were depleted of putrescine and spermidine was investigated. Only beta-methylated spermidine, like natural spermidine was capable of restoring the growth of L. donovani, while the remaining three analogues turned out to be inactive. Considering that alpha-methylated spermidine is a functionally active spermidine surrogate both in vivo and in vitro, this analogue can be considered as an antidote in the host-parasite system, especially in cases where inhibitors of polyamine biosynthesis are used for the therapy of leishmaniasis.     

Biomass of planktonic crustaceans and the food of young cyprinids in the littoral zone of Lake Balaton

The littoral zone of Lake Balaton and its periphyton-zooplankton-fish communities have been investigated intensively in recent years. Total average number of crustacean plankton varied from 36 to 126 ind l^–1, their biomass from 0.49 to 1.86 mg ww l^–1 month^–1 at different areas of the littoral zone. In general, these values for the above parameters were higher in hypertrophic areas. 23 fish species occurred in the littoral zone with cyprinids dominating. The seasonal food spectra of Y-O-Y roach (Rutilus rutilus), white bream (Blicca bjoerkna) and bream (Abramis brema) were based mainly on planktonic crustaceans and benthic/periphytic invertebrates. According to the frequency of occurrence of crustaceans and other invertebrates, the food composition of young cyprinids differed significantly in the NE and SW-basins of the lake.     

Comparisons of the molecular evolutionary process at rbcL and ndhF in the grass family (Poaceae)

We examine rate heterogeneity among evolutionary lineages of the grass family at two plasmid loci, ndhF and rbcL, and we introduce a method to determine whether patterns of rate heterogeneity are correlated between loci. We show both that rates of synonymous evolution are heterogeneous among grass lineages and that are heterogeneity is correlated between loci at synonymous sites. At nonsynonymous sites, the pattern of rate heterogeneity is not correlated between loci, primarily due to an aberrant pattern of rate heterogeneity at nonsynonymous sites of rbcL. We compare patterns of synonymous rate heterogeneity to predictors based on the generation time effect and the speciation rate hypotheses. Although there is some evidence for generation time effects, neither generation time effects nor speciation rates appear to be sufficient to explain patterns of rate heterogeneity in the grass plastid sequences.      

Interaction of rabbit muscle enolase and 3-phosphoglycerate mutase studied by ELISA and by batch gel filtration.

The interaction of rabbit skeletal muscle enolase and 3-phosphoglycerate mutase was detected by an ELISA test, a batch gel-filtration technique, and fluorescence anisotropy measurements, and the activity of enolase was determined to be a function of mutase concentration. The apparent dissociation constant of this enzyme complex is approximately 1 microM. This value seems to be independent of the presence (in fluorescence anisotropy measurements) or the absence (in activity as well as in ELISA experiments) of fluorescein isothiocyanate used widely as a label for determining the complex formation between enzymes in fluorescence anisotropy measurements.     

Preparation of mouse antiserum against isologous aggregated immunoglobulins and its effect on rosette forming cells]

A method of obtaining antisera against isologous aggregated mouse immunoglobulins is described. This serum designated MAAS blocked in vitro the antigen-binding receptors of the immune rosette-forming cells. MAAS was injected to mice immunized with SRBC. In comparision with the immunized mice given normal isologous serum rosette-forming B-cells were absent in the spleen of mice given MAAS at the peak of isologous response. But the antibody-forming cell count was not decreased under the influence of MAAS.     

Methylated analogs of spermine and spermidine as tools to investigate cellular functions of polyamines and enzymes of their metabolism

Biogenic amines spermine (Spm) and spermidine (Spd) are essential for cell growth. Polyamine analogs are widely used to investigate the enzymes of polyamine metabolism and the functions of spermine and spermidine in vitro and in vivo. It was demonstrated recently that α-methylated derivatives of Spm and Spd are able to fulfill the key cellular functions of polyamines, moreover, in some cases, the effects of (R) and (S) isomers were actually different. Using these α-methylated analogs of Spm and Spd, it turned possible to prevent the development of acute pancreatitis in SSAT-transgenic rats with controllable expression of the Spm/Spd N¹-acetyltransferase gene. The analogs made it possible to reveal dormant stereospecificity of polyamine oxidase, Spm oxidase, and deoxyhypusine synthase. An original approach was suggested to regulate the stereospecificity of polyamine oxidase. Depletion of the intracellular polyamine pool was found to have both hypusine-related consequences and consequences unrelated to posttranslational modification of the eukaryotic translation initiation factor eIF5A. Possible applications of a new family of C-methylated polyamine analogs for the investigation and regulation of polyamine metabolism in vitro and in vivo are discussed.     

Genomic aberrations in lung adenocarcinoma in never smokers

Background

Lung cancer in never smokers would rank as the seventh most common cause of cancer death worldwide.

Methods and Findings

We performed high-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in sixty never smokers and identified fourteen new minimal common regions (MCR) of gain or loss, of which five contained a single gene (MOCS2, NSUN3, KHDRBS2, SNTG1 and ST18). One larger MCR of gain contained NSD1. One focal amplification and nine gains contained FUS. NSD1 and FUS are oncogenes hitherto not known to be associated with lung cancer. FISH showed that the amplicon containing FUS was joined to the next telomeric amplicon at 16p11.2. FUS was over-expressed in 10 tumors with gain of 16p11.2 compared to 30 tumors without that gain. Other cancer genes present in aberrations included ARNT, BCL9, CDK4, CDKN2B, EGFR, ERBB2, MDM2, MDM4, MET, MYC and KRAS. Unsupervised hierarchical clustering with adjustment for false-discovery rate revealed clusters differing by the level and pattern of aberrations and displaying particular tumor characteristics. One cluster was strongly associated with gain of MYC. Another cluster was characterized by extensive losses containing tumor suppressor genes of which RB1 and WRN. Tumors in that cluster frequently harbored a central scar-like fibrosis. A third cluster was associated with gains on 7p and 7q, containing ETV1 and BRAF, and displayed the highest rate of EGFR mutations. SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity.

Conclusions

The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers.     

Increased loss of duplicated genes in streptomycin-resistant (strA) mutants of Escherichia coli k-12.

The recombination-dependent loss of a duplicated portion of the Escherichia coli chromosome is five- to tenfold greater in strains containing streptomycin resistance (strA) mutations than in the strA+ parental strain. Streptomycin (500 mug/ml) partially reverses the increase. These results suggest an interaction between strA mutations and recombination.