Vascular Endothelial Growth Factor Genetic Polymorphisms and Haplotypes in Women with Migraine

Vascular endothelial growth factor (VEGF) production is regulated by growth factors and inflammatory cytokines, and VEGF plays a role in migraine. We examined for the first time whether three functional polymorphisms in the promoter region of VEGF gene (C(-2578)A, G(-1154A), and G(-634C)) and VEGF haplotypes are associated with migraine. We studied 114 healthy women without migraine and 175 women with migraine (129 without aura, and 46 with aura). We found no differences in the distributions of VEGF genotypes and alleles (p > 0.05). However, the CAC haplotype was more frequent in controls than in migraine patients, and the AGC haplotype was more frequent in patients with migraine with aura than in controls (both p < 0.05). These findings suggest that VEGF haplotypes affect susceptibility to migraine.

A New Mouse Model for Marfan Syndrome Presents Phenotypic Variability Associated with the Genetic Background and Overall Levels of Fbn1 Expression

Marfan syndrome is an autosomal dominant disease of connective tissue caused by mutations in the fibrillin-1 encoding gene FBN1. Patients present cardiovascular, ocular and skeletal manifestations, and although being fully penetrant, MFS is characterized by a wide clinical variability both within and between families. Here we describe a new mouse model of MFS that recapitulates the clinical heterogeneity of the syndrome in humans. Heterozygotes for the mutant Fbn1 allele mg Delta(loxPneo), carrying the same internal deletion of exons 19-24 as the mg Delta mouse model, present defective microfibrillar deposition, emphysema, deterioration of aortic wall and kyphosis. However, the onset of a clinical phenotypes is earlier in the 129/Sv than in C57BL/6 background, indicating the existence of genetic modifiers of MFS between these two mouse strains. In addition, we characterized a wide clinical variability within the 129/Sv congenic heterozygotes, suggesting involvement of epigenetic factors in disease severity. Finally, we show a strong negative correlation between overall levels of Fbn1 expression and the severity of the phenotypes, corroborating the suggested protective role of normal fibrillin-1 in MFS pathogenesis, and supporting the development of therapies based on increasing Fbn1 expression.

Genetic variability and natural selection at the ligand domain of the Duffy binding protein in brazilian Plasmodium vivax populations

Background: Plasmodium vivax malaria is a major public health challenge in Latin America, Asia and Oceania, with 130-435 million clinical cases per year worldwide. Invasion of host blood cells by P. vivax mainly depends on a type I membrane protein called Duffy binding protein (PvDBP). The erythrocyte-binding motif of PvDBP is a 170 amino-acid stretch located in its cysteine-rich region II (PvDBP(II)), which is the most variable segment of the protein. Methods: To test whether diversifying natural selection has shaped the nucleotide diversity of PvDBP(II) in Brazilian populations, this region was sequenced in 122 isolates from six different geographic areas. A Bayesian method was applied to test for the action of natural selection under a population genetic model that incorporates recombination. The analysis was integrated with a structural model of PvDBP(II), and T-and B-cell epitopes were localized on the 3-D structure. Results: The results suggest that: (i) recombination plays an important role in determining the haplotype structure of PvDBP(II), and (ii) PvDBP(II) appears to contain neutrally evolving codons as well as codons evolving under natural selection. Diversifying selection preferentially acts on sites identified as epitopes, particularly on amino acid residues 417, 419, and 424, which show strong linkage disequilibrium. Conclusions: This study shows that some polymorphisms of PvDBP(II) are present near the erythrocyte-binding domain and might serve to elude antibodies that inhibit cell invasion. Therefore, these polymorphisms should be taken into account when designing vaccines aimed at eliciting antibodies to inhibit erythrocyte invasion.

Gene Expression Complex Networks: Synthesis, Identification, and Analysis

Thanks to recent advances in molecular biology, allied to an ever increasing amount of experimental data, the functional state of thousands of genes can now be extracted simultaneously by using methods such as cDNA microarrays and RNA-Seq. Particularly important related investigations are the modeling and identification of gene regulatory networks from expression data sets. Such a knowledge is fundamental for many applications, such as disease treatment, therapeutic intervention strategies and drugs design, as well as for planning high-throughput new experiments. Methods have been developed for gene networks modeling and identification from expression profiles. However, an important open problem regards how to validate such approaches and its results. This work presents an objective approach for validation of gene network modeling and identification which comprises the following three main aspects: (1) Artificial Gene Networks (AGNs) model generation through theoretical models of complex networks, which is used to simulate temporal expression data; (2) a computational method for gene network identification from the simulated data, which is founded on a feature selection approach where a target gene is fixed and the expression profile is observed for all other genes in order to identify a relevant subset of predictors; and (3) validation of the identified AGN-based network through comparison with the original network. The proposed framework allows several types of AGNs to be generated and used in order to simulate temporal expression data. The results of the network identification method can then be compared to the original network in order to estimate its properties and accuracy. Some of the most important theoretical models of complex networks have been assessed: the uniformly-random Erdos-Renyi (ER), the small-world Watts-Strogatz (WS), the scale-free Barabasi-Albert (BA), and geographical networks (GG). The experimental results indicate that the inference method was sensitive to average degree k variation, decreasing its network recovery rate with the increase of k. The signal size was important for the inference method to get better accuracy in the network identification rate, presenting very good results with small expression profiles. However, the adopted inference method was not sensible to recognize distinct structures of interaction among genes, presenting a similar behavior when applied to different network topologies. In summary, the proposed framework, though simple, was adequate for the validation of the inferred networks by identifying some properties of the evaluated method, which can be extended to other inference methods.

Construct and Compare Gene Coexpression Networks with DAPfinder and DAPview

Background: DAPfinder and DAPview are novel BRB-ArrayTools plug-ins to construct gene coexpression networks and identify significant differences in pairwise gene-gene coexpression between two phenotypes. Results: Each significant difference in gene-gene association represents a Differentially Associated Pair (DAP). Our tools include several choices of filtering methods, gene-gene association metrics, statistical testing methods and multiple comparison adjustments. Network results are easily displayed in Cytoscape. Analyses of glioma experiments and microarray simulations demonstrate the utility of these tools. Conclusions: DAPfinder is a new friendly-user tool for reconstruction and comparison of biological networks.

Adaptive Approach for a Maximum Entropy Algorithm in Ecological Niche Modeling

This paper presents an Adaptive Maximum Entropy (AME) approach for modeling biological species. The Maximum Entropy algorithm (MaxEnt) is one of the most used methods in modeling biological species geographical distribution. The approach presented here is an alternative to the classical algorithm. Instead of using the same set features in the training, the AME approach tries to insert or to remove a single feature at each iteration. The aim is to reach the convergence faster without affect the performance of the generated models. The preliminary experiments were well performed. They showed an increasing on performance both in accuracy and in execution time. Comparisons with other algorithms are beyond the scope of this paper. Some important researches are proposed as future works.

Mutually connected phase-locked loop networks: dynamical models and design parameters

Distribution of timing signals is an essential factor for the development of digital systems for telecommunication networks, integrated circuits and manufacturing automation. Originally, this distribution was implemented by using the master-slave architecture with a precise master clock generator sending signals to phase-locked loops (PLL) working as slave oscillators. Nowadays, wireless networks with dynamical connectivity and the increase in size and operation frequency of the integrated circuits suggest that the distribution of clock signals could be more efficient if mutually connected architectures were used. Here, mutually connected PLL networks are studied and conditions for synchronous states existence are analytically derived, depending on individual node parameters and network connectivity, considering that the nodes are nonlinear oscillators with nonlinear coupling conditions. An expression for the network synchronisation frequency is obtained. The lock-in range and the transmission error bounds are analysed providing hints to the design of this kind of clock distribution system.

COMPETITION AMONG EUCALYPTUS TREES DEPENDS ON GENETIC VARIATION AND RESOURCE SUPPLY

Genetic variation and environmental heterogeneity fundamentally shape the interactions between plants of the same species. According to the resource partitioning hypothesis, competition between neighbors intensifies as their similarity increases. Such competition may change in response to increasing supplies of limiting resources. We tested the resource partitioning hypothesis in stands of genetically identical (clone-origin) and genetically diverse (seed-origin) Eucalyptus trees with different water and nutrient supplies, using individual-based tree growth models. We found that genetic variation greatly reduced competitive interactions between neighboring trees, supporting the resource partitioning hypothesis. The importance of genetic variation for Eucalyptus growth patterns depended strongly on local stand structure and focal tree size. This suggests that spatial and temporal variation in the strength of species interactions leads to reversals in the growth rank of seed-origin and clone-origin trees. This study is one of the first to experimentally test the resource partitioning hypothesis for intergenotypic vs. intragenotypic interactions in trees. We provide evidence that variation at the level of genes, and not just species, is functionally important for driving individual and community-level processes in forested ecosystems.

Genetic structure and biology of Xylella fastidiosa strains causing disease in citrus and coffee in Brazil

Xylella fastidiosa is a vector-borne, plant-pathogenic bacterium that causes disease in citrus (citrus variegated chlorosis [CVC]) and coffee (coffee leaf scorch [CLS]) plants in Brazil. CVC and CLS occur sympatrically and share leafhopper vectors; thus, determining whether X. fastidiosa isolates can be dispersed from one crop to another and cause disease is of epidemiological importance. We sought to clarify the genetic and biological relationships between CVC- and CLS-causing X. fastidiosa isolates. We used cross-inoculation bioassays and microsatellite and multilocus sequence typing (MLST) approaches to determine the host range and genetic structure of 26 CVC and 20 CLS isolates collected from different regions in Brazil. Our results show that citrus and coffee X. fastidiosa isolates are biologically distinct. Cross-inoculation tests showed that isolates causing CVC and CLS in the field were able to colonize citrus and coffee plants, respectively, but not the other host, indicating biological isolation between the strains. The microsatellite analysis separated most X. fastidiosa populations tested on the basis of the host plant from which they were isolated. However, recombination among isolates was detected and a lack of congruency among phylogenetic trees was observed for the loci used in the MLST scheme. Altogether, our study indicates that CVC and CLS are caused by two biologically distinct strains of X. fastidiosa that have diverged but are genetically homogenized by frequent recombination.

Genetic structure and mating system of Euterpe edulis Mart. populations: A comparative analysis using microsatellite and allozyme markers

A comparative study between microsatellite and allozyme markers was conducted on the genetic structure and mating system in natural populations of Euterpe edulis Mart. Three cohorts, including seedlings, saplings, and adults, were examined in 4 populations using 10 allozyme loci and 10 microsatellite loci. As expected, microsatellite markers had a much higher degree of polymorphism than allozymes, but estimates of multilocus outcrossing rate ((t) over cap (m) = 1.00), as well as estimates of genetic structure (F(IS), G(ST)), were similar for the 2 sets of markers. Estimates of R(ST), for microsatellites, were higher than those of GST, but results of both statistics revealed a close agreement for the genetic structure of the species. This study provides support for the important conclusion that allozymes are still useful and reliable markers to estimate population genetic parameters. Effects of sample size on estimates from hypervariable loci are also discussed in this paper.

Genetic Diversity and a PCR-Based Method for Xanthomonas axonopodis Detection in Passion Fruit

Xanthomonas axonopodis pv. passiflorae causes bacterial spot in passion fruit. It attacks the purple and yellow passion fruit as well as the sweet passion fruit. The diversity of 87 isolates of pv. passiflorae collected from across 22 fruit orchards in Brazil was evaluated using molecular profiles and statistical procedures, including an unweighted pair-group method with arithmetical averages-based dendrogram, analysis of molecular variance (AMOVA), and an assigning test that provides information on genetic structure at the population level. Isolates from another eight pathovars were included in the molecular analyses and all were shown to have a distinct repetitive sequence-based polymerase chain reaction profile. Amplified fragment length polymorphism technique revealed considerable diversity among isolates of pv. passiflorae, and AMOVA showed that most of the variance (49.4%) was due to differences between localities. Cluster analysis revealed that most genotypic clusters were homogeneous and that variance was associated primarily with geographic origin. The disease adversely affects fruit production and may kill infected plants. A method for rapid diagnosis of the pathogen, even before the disease symptoms become evident, has value for producers. Here, a set of primers (Xapas) was designed by exploiting a single-nucleotide polymorphism between the sequences of the intergenic 16S-23S rRNA spacer region of the pathovars. Xapas was shown to effectively detect all pv. passiflorae isolates and is recommended for disease diagnosis in passion fruit orchards.

Genetic diversity and plant-growth related features of Burkholderia spp. from sugarcane roots

Brazil is the largest sugarcane producer in the world, mainly due to the development of different management strategies. Recently, microbial-plant related studies revealed that bacterial isolates belonging to the genus Burkholderia are mainly associated with this plant and are responsible for a range of physiological activity. In this study, we properly evaluate the physiological activity and genetic diversity of endophytic and rhizospheric Burkholderia spp. isolates from sugarcane roots grown in the field in Brazil. In total, 39 isolates previously identified as Burkholderia spp. were firstly evaluated for the capability to fix nitrogen, produce siderophores, solubilise inorganic phosphates, produce indole-acetic acid and inhibit sugarcane phytopathogens in vitro. These results revealed that all isolates present at least two positive evaluated activities. Furthermore, a phylogenetic study was carried out using 16S rRNA and gyrB genes revealing that most of the isolates were affiliated with the Burkholderia cepacia complex. Hence, a clear separation given by endophytic or rhizospheric niche occupation was not observed. These results presented an overview about Burkholderia spp. isolates from sugarcane roots and supply information about the physiological activity and genetic diversity of this genus, given direction for further studies related to achieve more sustainable cultivation of sugarcane.

Genetic structure and evolution of species in the mangrove genus Avicennia (Avicenniaceae) in the Indo-West Pacific

Allozyme variation in species of the mangrove genus Avicennia was screened in 25 populations collected from 22 locations in the Indo-West Pacific and eastern North America using 11 loci. Several fixed gene differences supported the specific status of Avicennia alba, A. integra, A. marina, and A. rumphiana from the Indo-West Pacific, and A. germinans from the Atlantic-East Pacific. The three varieties of A. marina, var. marina, var. eucalyptifolia, and var. australasica, had higher genetic similarities (Nei's I) and no fixed gene differences, confirming their conspecific status. Strong genetic structuring was observed in A. marina, with sharp changes in gene frequencies at the geographical margins of varietal distributions. The occurrence of alleles found otherwise in only one variety, in only immediately adjacent populations of another variety, provided evidence of introgession between varieties. The varieties appear to have diverged recently in the Pleistocene and are apparently not of ancient Cretaceous origin, as suggested earlier. Despite evidence of high degrees of outcrossing, gene flow among populations was relatively low (N(e)m less than or equal to 1-2), except where populations were geographically continuous, questioning assumptions that these widespread mangrove species achieve high levels of long-distance dispersal.

Social structures, genetic structures and dispersal strategies in Australian rabbit (Oryctolagus cuniculus) populations

In this study, the pattern of movement of young male and female rabbits and the genetic structures present in adult male and female populations in four habitats was examined. The level of philopatry in young animals was found to vary between 18-90% for males and 32-95% for females in different populations. It was skewed, with more males dispersing than females in some but not all populations. Analysis of allozyme data using spatial autocorrelation showed that adult females from the same social group, unlike males, were significantly related in four of the five populations studied. Changes in genetic structure and rate of dispersal were measured before and during the recovery of a population that was artificially reduced in size. There were changes in the rate and distance of dispersal with density and sex. Subadults of both sexes moved further in the first year post crash (low density) than in the following years. While the level of dispersal for females was lower than that of the males for the first 3 years, thereafter (high density) both sexes showed similar, low levels of dispersal (20%). The density at which young animals switch behaviour between dispersal and philopatry differed for males and females. The level of genetic structuring in adult females was high in the precrash population, reduced in the first year post crash and undetectable in the second year. Dispersal behaviour of rabbits both affects the genetic structure of the population and changes with conditions. Over a wide range of levels of philopatry, genetic structuring is present in the adult female, but not the male population. Consequently, though genetic structuring is present, it does not lead to inbreeding. More long-distance movements are found in low-density populations, even though vacant warrens are available near birth warrens. The distances moved decreased as density increased. Calculation of the effective population size (N-e) shows that changes in dispersal distance offset changes in density, so that N-e remains constant.