The role of the TRAF-interacting protein in proliferation and differentiation.

Ubiquitination of proteins is a post-translational modification, which decides on the cellular fate of the protein. Addition of ubiquitin moieties to proteins is carried out by the sequential action of three enzymes: E1, ubiquitin-activating enzyme; E2, ubiquitin-conjugating enzyme; and E3, ubiquitin ligase. The TRAF-interacting protein (TRAIP, TRIP, RNF206) functions as Really Interesting New Gene (RING)-type E3 ubiquitin ligase, but its physiological substrates are not yet known. TRAIP was reported to interact with TRAF [tumor necrosis factor (TNF) receptor-associated factors] and the two tumor suppressors CYLD and Syk (spleen tyrosine kinase). Ectopically expressed TRAIP was shown to inhibit nuclear factor-kappa B (NF-κB) signalling. However, recent results suggested a role for TRAIP in biological processes other than NF-κB regulation. Knock-down of TRAIP in human epidermal keratinocytes repressed cellular proliferation and induced a block in the G1/S phase of the cell cycle without affecting NF-κB signalling. TRAIP is necessary for embryonal development as mutations affecting the Drosophila homologue of TRAIP are maternal effect-lethal mutants, and TRAIP knock-out mice die in utero because of aberrant regulation of cell proliferation and apoptosis. These findings underline the tight link between TRAIP and cell proliferation. In this review, we summarize the data on TRAIP and put them into a larger perspective regarding the role of TRAIP in the control of tissue homeostasis.

Epistasis and maternal effects in experimental adaptation to chronic nutritional stress in Drosophila.

Based on ecological and metabolic arguments, some authors predict that adaptation to novel, harsh environments should involve alleles showing negative (diminishing return) epistasis and/or that it should be mediated in part by evolution of maternal effects. Although the first prediction has been supported in microbes, there has been little experimental support for either prediction in multicellular eukaryotes. Here we use a line-cross design to study the genetic architecture of adaptation to chronic larval malnutrition in a population of Drosophila melanogaster that evolved on an extremely nutrient-poor larval food for 84 generations. We assayed three fitness-related traits (developmental rate, adult female weight and egg-to-adult viability) under the malnutrition conditions in 14 crosses between this selected population and a nonadapted control population originally derived from the same base population. All traits showed a pattern of negative epistasis between alleles improving performance under malnutrition. Furthermore, evolutionary changes in maternal traits accounted for half of the 68% increase in viability and for the whole of 8% reduction in adult female body weight in the selected population (relative to unselected controls). These results thus support both of the above predictions and point to the importance of nonadditive effects in adaptive microevolution.

Genetic control of potassium content of common bean seeds

The objective of this work was to investigate possible maternal effects on potassium content of common bean seeds, as well as to estimate the heritability and selection gains in early hybrid generations for this character and to evaluate the efficiency of genetic selection to improve the nutritional quality of common bean (Phaseolus vulgaris). Crosses with four cultivars from the Mesoamerican gene pool yielded the reciprocal F1 and F2 generations and the backcrossed populations (BCP1 and BCP2). The potassium content of the progenies was measured via nitric‑perchloric digestion and flame photometry. The potassium content in the tested progenies varied from 6.0 to 14.9 g kg-1 dry matter, and no significant maternal effect was observed. The narrow-sense heritability ranged from low (33.26%) to intermediate (43.05%). Partial dominance was observed for low potassium content in the seeds. No increase in potassium content was obtained through selection. Breeding common bean plants for increasing potassium content in seeds may be difficult because the local environment strongly influences the character.

Genetic control of iron concentration in Mesoamerican and Andean common bean seeds

The objective of this work was to evaluate the main differences in the genetic control of the iron concentration in Mesoamerican and Andean common bean seeds, in early generations, and to select recombinants with a high iron concentration in the seeds. F1, F1 reciprocal, F2, F2 reciprocal, and backcross (BC11 and BC12) generations were produced by crosses between Mesoamerican (CNFP 10104 x CHC 01-175) and Andean (Cal 96 x Hooter) inbred lines. The expression of significant maternal effect was observed for the Mesoamerican gene pool. Iron concentration was higher in the seed coat of Mesoamerican common bean seeds (54.61 to 67.92%) and in the embryo of Andean common bean seeds (69.40 to 73.44%). High broad-sense heritability was obtained for iron concentration in Mesoamerican and Andean common bean seeds. Gains with the selection of higher magnitude, from 20.39 to 24.58%, are expected in Mesoamerican common bean seeds. Iron concentration in common bean seeds showed a continuous distribution in F2, which is characteristic of quantitative inheritance in Mesoamerican and Andean common bean seeds. Recombinants with high iron concentration in seeds can be selected in both Mesoamerican and Andean common bean hybrids.

Acute and short-term insulin-induced molecular adaptations of GLUT2 gene expression in the renal cortex of diabetic rats

Increased GLUT2 gene expression in the renal proximal tubule of diabetic rats is an adaptive condition, which may be important in the diabetic nephropathy development. We investigated the effects of insulin treatment upon the renal GLUT2 overexpression of diabetic rats. Acute treatment, surprisingly, induced a rapid further increase in GLUT2 mRNA content. Twelve hours after insulin injection, GLUT2 mRNA was twice the value of saline-injected rats (P < 0.001), when GLUT2 protein remained unchanged. In response to short-term treatment, both GLUT2 mRNA and protein were increased in 1-day treated rats (P < 0.05 versus saline-injected), decreasing after that, and reaching, within 6 days, values close to those of non-diabetic rats. Concluding, insulin treatment induced: initially, an additional upregulation of GLUT2 gene expression, involving posttranscriptional modulation; thereafter, downregulation of GLUT2 expression, which returns to non-diabetic levels. The former may be related to increased insulin concentration, the latter may be due to glycemic control. © 2005 Elsevier B.V. All rights reserved.

Estudo da interação genótipo-ambiente em rebanhos da raça Nelore na Amazônia Legal

Dados de pesos padronizados aos 120 (P120), 210 (P210), 450 (P450) dias de idade, perímetro escrotal aos 450 dias de idade (PE450) e idade ao primeiro parto (IPP), de 211.744 registros de animais Nelore, provenientes de fazenda localizadas na região da Amazônia Legal, foram utilizados na análise. O efeito da interação genótipo-ambiente foi estudado por meio de estimativas de herdabilidade e de correlações entre classificações, comparando os animais da Amazônia Legal com a base geral de animais do PMGRN – Nelore Brasil. As análises bi-característica consideraram o P120 como característica-âncora, com P210, P450 e PE450. O modelo de análise considerou grupo de contemporâneos de P120, P210, P450 e da classe de idade da vaca ao parto (CIVP) como efeitos fixos e os efeitos aleatórios genéticos aditivos diretos, maternos e residuais. Nas análises de P120 com P450 e com PE450 foi desconsiderado o efeito materno no modelo. A covariância aditivo-materna foi fixada em zero, conforme protocolo estabelecido nas análises do PMGRN – Nelore Brasil. A característica IPP foi analisada separadamente, em análise de característica única e considerando como efeito fixo o GCIPP e como aleatórios os efeitos aditivos genéticos e residual. Para realizar a comparação entre classificações, por meio do procedimento PROC CORR opção spearman do SAS. As estimativas de herdabilidade para P120, P210, P450, PE450 e IPP nos dados da Amazônia Legal foram: 0,20 a 0,49; 0,21; 0,48; 0,45 e 0,21, respectivamente, e nos dados gerais do PMGRN – Nelore Brasil foram: 0,23; 0,25; 0,34; 0,43 e 0,11, respectivamente. As correlações entre classificações de rank para P120, P210, P450, PE450 e IPP foram iguais a 0,77; 0,79; 0,82; 0,78 e 0,38, respectivamente. As análises da interação genótipo-ambiente evidenciaram maiores efeitos sobre os aspectos maternos, de peso ao sobreano e IPP, enquanto que as correlações entre classificações mostraram fortes evidências de interação genótipo-ambiente em quase todas as características estudadas.

Single early prenatal lipopolysaccharide exposure impairs striatal monoamines and maternal care in female rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Drosophila valois encodes a divergent WD protein that is required for Vasa localization and Oskar protein accumulation

valois (vls) was identified as a posterior group gene in the initial screens for Drosophila maternal-effect lethal mutations. Despite its early genetic identification, it has not been characterized at the molecular level until now. We show that vls encodes a divergent WD domain protein and that the three available EMS-induced point mutations cause premature stop codons in the vls ORF. We have generated a null allele that has a stronger phenotype than the EMS mutants. The vlsnull mutant shows that vls+ is required for high levels of Oskar protein to accumulate during oogenesis, for normal posterior localization of Oskar in later stages of oogenesis and for posterior localization of the Vasa protein during the entire process of pole plasm assembly. There is no evidence for vls being dependent on an upstream factor of the posterior pathway, suggesting that Valois protein (Vls) instead acts as a co-factor in the process. Based on the structure of Vls, the function of similar proteins in different systems and our phenotypic analysis, it seems likely that vls may promote posterior patterning by facilitating interactions between different molecules.

Map positions of third chromosomal female sterile and lethal mutations of Drosophila melanogaster

Chromosomal mutations induced by ethyl methanesulfonate (EMS) treatment can cause female sterility or maternal-effect lethality in Drosophila. EMS is particularly useful to researchers because it creates mutations independent of position effects. However, because researchers have little control over the chromosomal site of mutation, post-mutagenic genetic mapping is required to determine the cytological location of the mutation. To make a valuable set of mutants more useful to the research community, we have mapped the uncharacterized part of the female-sterile – maternal-effect lethal Tübingen collection. We mapped 49 female-sterile – maternal-effect lethal alleles and 72 lethal alleles to individual deficiency intervals on the third chromosome. In addition, we analyzed the phenotype of ovaries resulting from female sterile mutations. The observed phenotypes range from tumorous ovaries and early blocks in oogenesis, to later blocks, slow growth, blocks in stage 10, to apparently full development of the ovary. The mapping and phenotypic characterization of these 121 mutations provide the necessary information for the researcher to consider a specific mutant as a candidate for their gene of interest.Key words: Drosophila melanogaster, oogenesis, female sterile, maternal-effect lethal, EMS-induced mutations.

Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling

Mutations in the human presenilin genes PS1 and PS2 cause early-onset Alzheimer’s disease. Studies in Caenorhabditis elegans and in mice indicate that one function of presenilin genes is to facilitate Notch-pathway signaling. Notably, mutations in the C. elegans presenilin gene sel-12 reduce signaling through an activated version of the Notch receptor LIN-12. To investigate the function of a second C. elegans presenilin gene hop-1 and to examine possible genetic interactions between hop-1 and sel-12, we used a reverse genetic strategy to isolate deletion alleles of both loci. Animals bearing both hop-1 and sel-12 deletions displayed new phenotypes not observed in animals bearing either single deletion. These new phenotypes—germ-line proliferation defects, maternal-effect embryonic lethality, and somatic gonad defects—resemble those resulting from a reduction in signaling through the C. elegans Notch receptors GLP-1 and LIN-12. Thus SEL-12 and HOP-1 appear to function redundantly in promoting Notch-pathway signaling. Phenotypic analyses of hop-1 and sel-12 single and double mutant animals suggest that sel-12 provides more presenilin function than does hop-1.

Induction and transmission of Bacillus thuringiensis tolerance in the flour moth Ephestia kuehniella

The use of Bacillus thuringiensis (Bt) endotoxins to control insect vectors of human diseases and agricultural pests is threatened by the possible evolution of resistance in major pest species. In addition to high levels of resistance produced by receptor insensitivity (5, 16, 17), several cases of tolerance to low to medium levels of toxin have been reported in laboratory colonies of lepidopteran species (3, 18). Because the molecular basis of some of these cases of tolerance to the toxin are not known, we explored alternative mechanisms. Here, we present evidence that tolerance to a Bt formulation in a laboratory colony of the flour moth Ephestia kuehniella can be induced by preexposure to a low concentration of the Bt formulation and that the tolerance correlates with an elevated immune response. The data also indicate that both immune induction and Bt tolerance can be transmitted to offspring by a maternal effect and that their magnitudes are determined by more than one gene.

Avaliação genética multirracial para ganho de peso pré-desmama em bovinos de uma população composta

Objetivou-se neste trabalho estudar modelos com efeitos não-aditivos diretos e maternos em uma população composta em clima tropical, tentando minimizar esses efeitos para obtenção dos valores genéticos dos animais avaliados. Foram utilizados dados de animais de uma população composta, por meio da comparação de três modelos que incluíram os efeitos fixos de grupo contemporâneo, ordem de parto e heterose direta e materna e os efeitos aleatórios de efeito genético aditivo direto e materno. As análises foram realizadas em duas etapas; na primeira foram estudadas as estimativas dos efeitos raciais e de heterose individual e materna e na segunda etapa, calculadas as variâncias, herdabilidades e os valores genéticos dos animais. O efeito materno, quando não foi considerado no modelo, pareceu superestimar o efeito aditivo racial. Os efeitos aditivos raciais, racial materno e de heterose individual e materna influenciaram significativamente o ganho médio diário no pré-desmame, obtendo-se diferentes estimativas entre os tipos biológicos. Considerando o arquivo de dados corrigidos para os efeitos não-aditivos diretos e maternos, as herdabilidades direta e materna foram de 0,22 e 0,20, respectivamente. Os efeitos racial materno e de heterose individual e materna foram importantes fontes de variação para o ganho médio diário no pré-desmame e devem ser considerados durante a avaliação genética de uma população multirracial.

Genetic parameters for pre-weaning traits in Braunvieh cattle

The objective of this study was to estimate genetic parameters for pre-weaning traits of Braunvieh cattle raised under tropical conditions in Brazil. The weight and weight gain parameters were birth weight (BW, N = 9955), weight at 120 days of age (W120, N = 5901), weaning weight at 205 days (WW, N = 6970), weight gain from birth to 205 days (GAIN205, N = 6013), weight gain from birth to 120 days (GAIN120, N = 5135), and weight gain from 120 to 205 days (GAIN85, N = 4482). Variance components were estimated using the animal model with the MTDFREML software. The relationship matrix included 35,188 animals; phenotypic measures were available for 18,688. Direct and maternal heritability increased from birth to weaning, with estimates of 0.23 +/- 0.037, 0.25 +/- 0.050, 0.41 +/- 0.059 for direct heritability for BW, W120 and WW, respectively, 0.08 +/- 0.012, 0.15 +/- 0.032, 0.22 +/- 0.036 for maternal genetic effects, and 0.18, 0.14 and 0.16 for total heritability estimates. For pre-weaning gains, estimates of heritability were 0.36 +/- 0.059, 0.30 +/- 0.059, 0.12 +/- 0.035 for direct genetic effects of the traits GAIN205, GAIN120 and GAIN85, respectively, 0.23 +/- 0.038, 0.17 +/- 0.037, 0.03 +/- 0.029 for estimates of maternal heritability, and 0.12, 0.13, 0.16 for total heritability, respectively. Genetic correlations between weights were greater between measures taken at shorter intervals. This information can be used to optimize the design of programs for genetic improvement of Braunvieh cattle raised under tropical conditions.

Genetic parameters for postweaning traits in Braunvieh cattle

Genetic parameters for traits related to postweaning growth in Braunvieh cattle, reared under tropical and sub-tropical conditions in Brazil, were studied. Weight traits were weight at 365 days of age (W365, N = 4055), at 450 days (W450, N = 3453), and at 550 days (W550, N = 1946), while weight gains were gain from weaning to 365 days of age (WGW365, N = 3060), from weaning to 450 days (WGW450, N = 2764), from weaning to 550 days (WGW550, N = 1531), from 365 to 550 days of age (WG365550, N = 1528), from 365 to 450 days (WG365450, N = 2401), and from 450 to 550 days (WG450550, N = 1563). A full animal model was used for estimating the variance components, using the MTDFREML software. The dataset contained 18,688 animals with phenotypic measures and 35,188 animals in the relationship matrix. Heritability estimates for postweaning weights decreased with age. For W365, W450 and W550, respectively, the direct heritability estimates were 0.29 +/- 0.061, 0.25 +/- 0.057, 0.16 +/- 0.060, maternal heritability was 0.20 +/- 0.035, 0.18 +/- 0.035, 0.13 +/- 0.052, and total heritability was 0.30, 0.35, 0.26. In this breed, maternal influence was found to be important up to 550 days of age. The greater genetic correlations between weights were observed for weights measured at shorter intervals. A large environmental effect was observed for weight gain between weaning and 550 days; this effect was greater for the gains between 365 and 550 days.

Comparison of different models to estimate genetic parameters for carcass traits in a commercial broiler line

The effect of genetic and non-genetic factors for carcass, breast meat and leg weights, and yields of a commercial broiler line were investigated using the restricted maximum likelihood method, considering four different animal models, including or excluding maternal genetic effect with covariance between direct and maternal genetic effects, and maternal permanent environmental effect. The likelihood ratio test was used to determine the most adequate model for each trait. For carcass, breast, and leg weight, and for carcass and breast yield, maternal genetic and permanent environmental effects as well as the covariance between direct and maternal genetic effects were significant. The estimates of direct and maternal heritability were 0.17 and 0.04 for carcass weight, 0.26 and 0.06 for breast weight, 0.22 and 0.02 for leg weight, 0.32 and 0.02 for carcass yield, and 0.52 and 0.04 for breast yield, respectively. For leg yield, maternal permanent environmental effect was important, in addition to direct genetic effects. For that trait, direct heritability and maternal permanent environmental variance as a proportion of the phenotypic variance were 0.43 and 0.02, respectively. The results indicate that ignoring maternal effects in the models, even though they were of small magnitude (0.02 to 0.06), tended to overestimate direct genetic variance and heritability for all traits.