The GP problem: quantifying gene-to-phenotype relationships

In this paper we refer to the gene-to-phenotype modeling challenge as the GP problem. Integrating information across levels of organization within a genotype-environment system is a major challenge in computational biology. However, resolving the GP problem is a fundamental requirement if we are to understand and predict phenotypes given knowledge of the genome and model dynamic properties of biological systems. Organisms are consequences of this integration, and it is a major property of biological systems that underlies the responses we observe. We discuss the E(NK) model as a framework for investigation of the GP problem and the prediction of system properties at different levels of organization. We apply this quantitative framework to an investigation of the processes involved in genetic improvement of plants for agriculture. In our analysis, N genes determine the genetic variation for a set of traits that are responsible for plant adaptation to E environment-types within a target population of environments. The N genes can interact in epistatic NK gene-networks through the way that they influence plant growth and development processes within a dynamic crop growth model. We use a sorghum crop growth model, available within the APSIM agricultural production systems simulation model, to integrate the gene-environment interactions that occur during growth and development and to predict genotype-to-phenotype relationships for a given E(NK) model. Directional selection is then applied to the population of genotypes, based on their predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a plant-breeding program. The outcomes of the simulated breeding are evaluated across cycles of selection in terms of the changes in allele frequencies for the N genes and the genotypic and phenotypic values of the populations of genotypes.

Rooting of hardwood cuttings of Roxo de Valinhos fig (Ficus carica L.) with different propagation strategies

The objective of this study was to evaluate the substrate, cuttings collection time, the position and the cutting depth, and the propagation environment on rooting of 'Purple Valinhos' fig tree cuttings in Southwestern Paraná, Brazil. Two experiments were carried out at UTFPR, Câmpus Dois Vizinhos, with hardwoods cuttings from Roxo de Valinhos fig tree. The first experiment used a randomized block design, in 3 x 3 x 2 factorial (substrate x environment x collection time), with four replications of 10 cuttings per plot. The cuttings were collected in the first fifteen days of July and August. The substrates were sand, soil and the mixture of these [1:1 (v / v)]. The environments used were open sky, tunnel with plastic cover and tunnel with half-shade black net cover. The second experiment used a randomized block design, 2 x 2 x 3 factorial (shoot cutting position x soil cover x shoot cutting depth), with four replications of 12 cuttings per plot. In the factor position, the vertically (0 º inclination) and inclined (45 º inclination) shoot cuttings were evaluated. Soil cover was tested with mulching plastic cover or not. The tested depths were 1/3, 1/2 and 2/3 in relation to the total length of the shoot cutting. In both experiments, the following were analyzed: rooting and mortality indices, number of leaves and primary shoots, length of the three largest roots per cutting. It was conclude that, the protected environment with plastic cover on sand as substrate must recommended for the rooting of fig estaca, collecting them in the first half of July. The inclination position and cutting depth of the estaca and the substrate coverage with plastic mulching did not influence the results.

Seleção de genótipos de trigo para rendimento de grãos e qualidade de panificação em ensaios multiambientes

O objetivo deste estudo foi selecionar linhagens de trigo para qualidade de panificação e para rendimento de grãos (RG), em ensaios multiambientes, e identificar ambientes de teste ideais para a seleção. Foram avaliados 39 genótipos de trigo, sendo 18 linhagens e nove cultivares testemunhas, em 2010, e 11 linhagens e quatro cultivares testemunhas, em 2011, no Estado do Paraná. Algumas linhagens e locais não foram repetidos entre os dois anos. O delineamento experimental utilizado foi o de blocos casualizados, com três repetições. A metodologia, em gráfico biplot GGE (Genotype and Genotype-by-Environment), foi utilizada para a avaliação de genótipos e ambientes de teste. Na safra 2010, os locais de Nova Fátima, Pitangueiras e Ventania foram discriminantes (maximizaram a expressão do RG e diferenciação entre genótipos) e representativos do conjunto de ambientes avaliados. Em 2011, Rolândia e Astorga destacaram-se como ambientes ideais para seleção simultânea para RG e qualidade de panificação. As linhagens BIO-08528 e BIO-08228 foram classificadas como genótipos ideais para o RG e a concentração proteica dos grãos (CPG), respectivamente. Na safra 2011, as linhagens BIO-10161 e BIO-10141 foram superiores para RG e para qualidade de panificação, respectivamente. O teste de sedimentação SDS e a CPG correlacionaram-se entre si (r = 0,61**) e foram moderadamente associados com a força de glúten (r = 0,49** e 0,74**), indicando que podem ser utilizados na seleção indireta para qualidade de panificação.

Percepções de doença e tratamento, estado emocional e satisfação nos cuidados de saúde em imagiologia

Mestrado em Intervenção Sócio-Organizacional na Saúde - Área de especialização: Políticas de Administração e Gestão de Serviços de Saúde.

O meio envolvente como um contributo para a ação pedagógica

Relatório da Prática Profissional Supervisionada Mestrado em Educação Pré-Escolar

Contribuição da susceptibilidade genética e do contexto ambiental na representação da vinculação em crianças em idade pré-escolar

Dissertação de mestrado integrado em Psicologia

Aging and motor programming: differential effects according to the selection of action

There are controversial reports about the effect of aging on movement preparation, and it is unclear to which extent cognitive and/or motor related cerebral processes may be affected. This study examines the age effects on electro-cortical oscillatory patterns during various motor programming tasks, in order to assess potential differences according to the mode of action selection. Twenty elderly (EP, 60-84 years) and 20 young (YP, 20-29 years) participants with normal cognition underwent 3 pre-cued response tasks (S1-S2 paradigm). S1 carried either complete information on response side (Full; stimulus-driven motor preparation), no information (None; general motor alertness), or required free response side selection (Free; internally-driven motor preparation). Electroencephalogram (EEG) was recorded using 64 surface electrodes. Alpha (8-12 Hz) desynchronization (ERD)/synchronization (ERS) and motor-related amplitude asymmetries (MRAA) were analyzed during the S1-S2 interval. Reaction times (RTs) to S2 were slower in EP than YP, and in None than in the other 2 tasks. There was an Age x Task interaction due to increased RTs in Free compared to Full in EP only. Central bilateral and midline activation (alpha ERD) was smaller in EP than YP in None. In Full just before S2, readiness to move was reflected by posterior midline inhibition (alpha ERS) in both groups. In Free, such inhibition was present only in YP. Moreover, MRAA showed motor activity lateralization in both groups in Full, but only in YP in Free. The results indicate reduced recruitment of motor regions for motor alertness in the elderly. They further show less efficient cerebral processes subtending free selection of movement in elders, suggesting reduced capacity for internally-driven action with age.

Tritordeum, wheat and triticale yield components under multi-local mediterranean drought conditions

The species x location interaction was of great importance in explaining the behaviour of genetic material. The study presented here shows, for the first time, the performance, under field conditions of the new tritordeum species, compared to wheat and triticale in a wide range of Mediterranean countries (Spain, Lebanon and Tunisia). The results obtained revealed that despite the diversity of environmental conditions, the main differences in yield were due to genotypes, especially to differences between species. The multi-local study with different growth conditions revealed important information about the water availability effect on yield. In the lowest yielding environments (Tunisia rainfed), Tritordeum and triticale yields were equivalent. However under better growth conditions (Spain), tritordeum yield was shown to be lower than wheat and triticale. Interestingly, when water limitation was extended during the pre-anthesis period, differences in tritordeum versus wheat-triticale yield rate were larger than when water stress occurred during anthesis. These variations were explained by the fact that kernel weight has been found as the limiting factor for yield determination in tritordeum, and a delay in the anthesis date may have been the cause for the low kernel weight and low yield under Mediterranean drought conditions. Such differences in yield between tritordeum and wheat or triticale could be explained by the fact that tritordeum is a relatively new species and far fewer resources have been devoted to its improvement when compared to wheat and triticale. Our results suggest that breeding efforts should be directed to an earlier anthesis date and a longer grain filling period. tritordeum proved to have possibilities to be grown under drought environments as a new crop, since its performance was quite close to wheat and triticale. Besides, it has qualitative added values that may improve farmers' income per unit land.

CYP3A5 and ABCB1 genes influence blood pressure and response to treatment, and their effect is modified by salt.

The permeability-glycoprotein efflux-transporter encoded by the multidrug resistance 1 (ABCB1) gene and the cytochromes P450 3A4/5 encoded by the CYP3A4/5 genes are known to interact in the transport and metabolism of many drugs. Recent data have shown that the CYP3A5 genotypes influence blood pressure and that permeability-glycoprotein activity might influence the activity of the renin-angiotensin system. Hence, these 2 genes may contribute to blood pressure regulation in humans. We analyzed the association of variants of the ABCB1 and CYP3A5 genes with ambulatory blood pressure, plasma renin activity, plasma aldosterone, endogenous lithium clearance, and blood pressure response to treatment in 72 families (373 individuals; 55% women; mean age: 46 years) of East African descent. The ABCB1 and CYP3A5 genes interact with urinary sodium excretion in their effect on ambulatory blood pressure (daytime systolic: P=0.05; nighttime systolic and diastolic: P<0.01), suggesting a gene-gene-environment interaction. The combined action of these genes is also associated with postproximal tubular sodium reabsorption, plasma renin activity, plasma aldosterone, and with an altered blood pressure response to the angiotensin-converting enzyme inhibitor lisinopril (P<0.05). This is the first reported association of the ABCB1 gene with blood pressure in humans and demonstration that genes encoding for proteins metabolizing and transporting drugs and endogenous substrates contribute to blood pressure regulation.

Natural genetic variation of root system architecture from Arabidopsis to Brachypodium: towards adaptive value.

Root system architecture is a trait that displays considerable plasticity because of its sensitivity to environmental stimuli. Nevertheless, to a significant degree it is genetically constrained as suggested by surveys of its natural genetic variation. A few regulators of root system architecture have been isolated as quantitative trait loci through the natural variation approach in the dicotyledon model, Arabidopsis. This provides proof of principle that allelic variation for root system architecture traits exists, is genetically tractable, and might be exploited for crop breeding. Beyond Arabidopsis, Brachypodium could serve as both a credible and experimentally accessible model for root system architecture variation in monocotyledons, as suggested by first glimpses of the different root morphologies of Brachypodium accessions. Whether a direct knowledge transfer gained from molecular model system studies will work in practice remains unclear however, because of a lack of comprehensive understanding of root system physiology in the native context. For instance, apart from a few notable exceptions, the adaptive value of genetic variation in root system modulators is unknown. Future studies should thus aim at comprehensive characterization of the role of genetic players in root system architecture variation by taking into account the native environmental conditions, in particular soil characteristics.

Genetik der essentiellen arteriellen Hypertonie [Essential hypertension - which genes can be held responsible for it?].

Hypertension is a common heritable cardiovascular risk factor. Some rare monogenic forms of hypertension have been described, but the majority of patients suffer from essential hypertension, for whom the underlying genetic mechanisms are not clear. Essential hypertension is a complex trait, involving multiple genes and environmental factors. Recently, progress in the identification of common genetic variants associated with essential hypertension has been made due to large-scale international collaborative projects. In this article we review the new research methods used as well as selected recent findings in this field.

Nonshivering thermogenesis capacity associated to mitochondrial DNA haplotypes and gender in the greater white-toothed shrew, Crocidura russula.

A selection gradient was recently suggested as one possible cause for a clinal distribution of mitochondrial DNA (mtDNA) haplotypes along an altitudinal transect in the greater white-toothed shrew, Crocidura russula (Ehinger et al. 2002). One mtDNA haplotype (H1) rare in lowland, became widespread when approaching the altitudinal margin of the distribution. As H1 differs from the main lowland haplotype by several nonsynonymous mutations (including on ATP6), and as mitochondria play a crucial role in metabolism and thermogenesis, distribution patterns might stem from differences in the thermogenic capacity of different mtDNA haplotypes. In order to test this hypothesis, we measured the nonshivering thermogenesis (NST) associated with different mtDNA haplotypes. Sixty-two shrews, half of which had the H1 haplotype, were acclimated in November at semioutdoor conditions and measured for NST throughout winter. Our results showed the crucial role of NST for winter survival in C. russula. The individuals that survived winter displayed a higher significant increase in NST during acclimation, associated with a significant gain in body mass, presumably from brown fat accumulation. The NST capacity (ratio of NST to basal metabolic rate) was exceptionally high for such a small species. NST was significantly affected by a gender x haplotype interaction after winter-acclimation: females bearing the H1 haplotype displayed a better thermogenesis at the onset of the breeding season, while the reverse was true for males. Altogether, our results suggest a sexually antagonistic cyto-nuclear selection on thermogenesis.

Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population

The manner by which genotype and environment affect complex phenotypes is one of the fundamental questions in biology. In this study, we quantified the transcriptome--a subset of the metabolome--and, using targeted proteomics, quantified a subset of the liver proteome from 40 strains of the BXD mouse genetic reference population on two diverse diets. We discovered dozens of transcript, protein, and metabolite QTLs, several of which linked to metabolic phenotypes. Most prominently, Dhtkd1 was identified as a primary regulator of 2-aminoadipate, explaining variance in fasted glucose and diabetes status in both mice and humans. These integrated molecular profiles also allowed further characterization of complex pathways, particularly the mitochondrial unfolded protein response (UPR(mt)). UPR(mt) shows strikingly variant responses at the transcript and protein level that are remarkably conserved among C. elegans, mice, and humans. Overall, these examples demonstrate the value of an integrated multilayered omics approach to characterize complex metabolic phenotypes.

Developmental and Environmental Regulation of Aquaporin Gene Expression across Populus Species: Divergence or Redundancy?

Aquaporins (AQPs) are membrane channels belonging to the major intrinsic proteins family and are known for their ability to facilitate water movement. While in Populus trichocarpa, AQP proteins form a large family encompassing fifty-five genes, most of the experimental work focused on a few genes or subfamilies. The current work was undertaken to develop a comprehensive picture of the whole AQP gene family in Populus species by delineating gene expression domain and distinguishing responsiveness to developmental and environmental cues. Since duplication events amplified the poplar AQP family, we addressed the question of expression redundancy between gene duplicates. On these purposes, we carried a meta-analysis of all publicly available Affymetrix experiments. Our in-silico strategy controlled for previously identified biases in cross-species transcriptomics, a necessary step for any comparative transcriptomics based on multispecies design chips. Three poplar AQPs were not supported by any expression data, even in a large collection of situations (abiotic and biotic constraints, temporal oscillations and mutants). The expression of 11 AQPs was never or poorly regulated whatever the wideness of their expression domain and their expression level. Our work highlighted that PtTIP1;4 was the most responsive gene of the AQP family. A high functional divergence between gene duplicates was detected across species and in response to tested cues, except for the root-expressed PtTIP2;3/PtTIP2;4 pair exhibiting 80% convergent responses. Our meta-analysis assessed key features of aquaporin expression which had remained hidden in single experiments, such as expression wideness, response specificity and genotype and environment interactions. By consolidating expression profiles using independent experimental series, we showed that the large expansion of AQP family in poplar was accompanied with a strong divergence of gene expression, even if some cases of functional redundancy could be suspected.

Reproductive and post-reproductive life history of wild-caught Drosophila melanogaster under laboratory conditions.

The life history of the fruit fly (Drosophila melanogaster) is well understood, but fitness components are rarely measured by following single individuals over their lifetime, thereby limiting insights into lifetime reproductive success, reproductive senescence and post-reproductive lifespan. Moreover, most studies have examined long-established laboratory strains rather than freshly caught individuals and may thus be confounded by adaptation to laboratory culture, inbreeding or mutation accumulation. Here, we have followed the life histories of individual females from three recently caught, non-laboratory-adapted wild populations of D. melanogaster. Populations varied in a number of life-history traits, including ovariole number, fecundity, hatchability and lifespan. To describe individual patterns of age-specific fecundity, we developed a new model that allowed us to distinguish four phases during a female's life: a phase of reproductive maturation, followed by a period of linear and then exponential decline in fecundity and, finally, a post-ovipository period. Individual females exhibited clear-cut fecundity peaks, which contrasts with previous analyses, and post-peak levels of fecundity declined independently of how long females lived. Notably, females had a pronounced post-reproductive lifespan, which on average made up 40% of total lifespan. Post-reproductive lifespan did not differ among populations and was not correlated with reproductive fitness components, supporting the hypothesis that this period is a highly variable, random 'add-on' at the end of reproductive life rather than a correlate of selection on reproductive fitness. Most life-history traits were positively correlated, a pattern that might be due to genotype by environment interactions when wild flies are brought into a novel laboratory environment but that is unlikely explained by inbreeding or positive mutational covariance caused by mutation accumulation.