Independent relations of left ventricular structure with the 24-hour urinary excretion of sodium and aldosterone.

Previous studies reported on the association of left ventricular mass index (LVMI) with urinary sodium or with circulating or urinary aldosterone. We investigated the independent associations of LVMI with the urinary excretion of both sodium and aldosterone. We randomly recruited 317 untreated subjects from a white population (45.1% women; mean age 48.2 years). Measurements included echocardiographic left ventricular (LV) properties, the 24-hour urinary excretion of sodium and aldosterone, plasma renin activity (PRA), and proximal (RNa(prox)) and distal (RNa(dist)) renal sodium reabsorption, assessed from the endogenous lithium clearance. In multivariable-adjusted models, we expressed changes in LVMI per 1-SD increase in the explanatory variables, while accounting for sex, age, systolic blood pressure, and the waist-to-hip ratio. LVMI increased independently with the urinary excretion of both sodium (+2.48 g/m(2); P=0.005) and aldosterone (+2.63 g/m(2); P=0.004). Higher sodium excretion was associated with increased mean wall thickness (MWT: +0.126 mm, P=0.054), but with no change in LV end-diastolic diameter (LVID: +0.12 mm, P=0.64). In contrast, higher aldosterone excretion was associated with higher LVID (+0.54 mm; P=0.017), but with no change in MWT (+0.070 mm; P=0.28). Higher RNa(dist) was associated with lower relative wall thickness (-0.81x10(-2), P=0.017), because of opposite trends in LVID (+0.33 mm; P=0.13) and MWT (-0.130 mm; P=0.040). LVMI was not associated with PRA or RNa(prox.) In conclusion, LVMI independently increased with both urinary sodium and aldosterone excretion. Increased MWT explained the association of LVMI with urinary sodium and increased LVID the association of LVMI with urinary aldosterone.

Symbolic trephinations and population structure

The sample examined consists of 19 skulls with symbolic trephinations and 86 skulls without trepanations dated from the X century. Skulls were all excavated in the Great Hungarian Plain in the Carpathian Basin, which was occupied by the Hungarian conquerors at the end of the IX century. The variations of 12 cranial dimensions of the trephined skulls were investigated and compared to the skulls without trepanations after performing a discriminant analysis. The classification results evince that the variability of non-trephined skulls shows a more homogeneous and a more characteristic picture of their own group than the trephined samples, which corresponds to the notion, formed by archaeological evidence and written historical sources, of a both ethnically and socially differing population of the Hungarian conquerors. According to historical research, a part of the population was of Finno-Ugric origin, while the military leading layer of society can be brought into connection with Turkic ethnic groups. All the same, individuals dug up with rich grave furniture and supposed to belong to this upper stratum of society are primarily characterized by the custom of symbolic trephination, and, as our results demonstrate, craniologically they seem to be more heterogeneous.

Population genetic structure of the major malaria vector Anopheles darlingi (Diptera: Culicidae) from the Brazilian Amazon, using microsatellite markers

The population genetic structure of Anopheles darlingi, the major human malaria vector in the Neotropics, was examined using seven microsatellite loci from nine localities in central and western Amazonian Brazil. High levels of genetic variability were detected (5-25 alleles per locus; H E = 0.519-0.949). There was deviation from Hardy-Weinberg Equilibrium for 59.79% of the tests due to heterozygote deficits, while the analysis of linkage disequilibrium was significant for only two of 189 (1.05%) tests, most likely caused by null alleles. Genetic differentiation (F ST = 0.001-0.095; Nm = 4.7-363.8) indicates that gene flow is extensive among locations < 152 km apart (with two exceptions) and reduced, but not absent, at a larger geographic scale. Genetic and geographic distances were significantly correlated (R² = 0.893, P < 0.0002), supporting the isolation by distance (IBD) model. The overall estimate of Ne was 202.4 individuals under the linkage disequilibrium model, and 8 under the heterozygote excess model. Analysis of molecular variance showed that nearly all variation (~ 94%) was within sample locations. The UPGMA phenogram clustered the samples geographically, with one branch including 5/6 of the state of Amazonas localities and the other branch the Acre, Rondônia, and remaining Amazonas localities. Taken together, these data suggest little genetic structure for An. darlingi from central and western Amazonian Brazil. These findings also imply that the IBD model explains nearly all of the differentiation detected. In practical terms, populations of An. darlingi at distances < 152 km should respond similarly to vector control measures, because of high gene flow.

Population structure of the malaria vector Anopheles darlingi in Rondônia, Brazilian Amazon, based on mitochondrial DNA

Anopheles darlingi is the most important Brazilian malaria vector, with a widespread distribution in the Amazon forest. Effective strategies for vector control could be better developed through knowledge of its genetic structure and gene flow among populations, to assess the vector diversity and competence in transmitting Plasmodium. The aim of this study was to assess the genetic diversity of An. darlingi collected at four locations in Porto Velho, by sequencing a fragment of the ND4 mitochondrial gene. From 218 individual mosquitoes, we obtained 20 different haplotypes with a diversity index of 0.756, equivalent to that found in other neotropical anophelines. The analysis did not demonstrate significant population structure. However, haplotype diversity within some populations seems to be over-represented, suggesting the presence of sub-populations, but the presence of highly represented haplotypes complicates this analysis. There was no clear correlation among genetic and geographical distance and there were differences in relation to seasonality, which is important for malarial epidemiology.

Copy number variation and chromatin structure

The functional consequences of structural variation in the human genome range from adaptation, to phenotypic variation, to predisposition to diseases. Copy number variation (CNV) was shown to influence the phenotype by modifying, in a somewhat dose-dependent manner, the expression of genes that map within them, as well as that of genes located on their flanks. To assess the possible mechanism(s) behind this neighboring effect, we compared histone modification status of cell lines from patients affected by Williams-Beuren, Williams-Beuren region duplication, Smith-Magenis or DiGeorge Syndrome and control individuals using a high-throughput version of chromatin immuno-precipitation method (ChIP), called ChlP-seq. We monitored monomethylation of lysine K20 on histone H4 and trimethylation of lysine K27 on histone H3, as proxies for open and condensed chromatin, respectively. Consistent with the changes in expression levels observed for multiple genes mapping on the entire length of chromosomes affected by structural variants, we also detected regions with modified histone status between samples, up- and downstream from the critical regions, up to the end of the rearranged chromosome. We also gauged the intrachromosomal interactions of these cell lines utilizing chromosome conformation capture (4C-seq) technique. We observed that a set of genes flanking the Williams-Beuren Syndrome critical region (WBSCR) were often looping together, possibly forming an interacting cluster with each other and the WBSCR. Deletion of the WBSCR disrupts the expression of this group of flanking genes, as well as long-range interactions between them and the rearranged interval. We conclude, that large genomic rearrangements can lead to changes in the state of the chromatin spreading far away from the critical region, thus possibly affecting expression globally and as a result modifying the phenotype of the patients. - Les conséquences fonctionnelles des variations structurelles dans le génome humain sont vastes, allant de l'adaptation, en passant par les variations phénotypiques, aux prédispositions à certaines maladies. Il a été démontré que les variations du nombre de copies (CNV) influencent le phénotype en modifiant, d'une manière plus ou moins dose-dépendante, l'expression des gènes se situant à l'intérieur de ces régions, mais également celle des gènes se trouvant dans les régions flanquantes. Afin d'étudier les mécanismes possibles sous-jacents à cet effet de voisinage, nous avons comparé les états de modification des histones dans des lignées cellulaires dérivées de patients atteints du syndrome de Williams-Beuren, de la duplication de la région Williams-Beuren, du syndrome de Smith-Magenis ou du syndrome de Di- George et d'individus contrôles en utilisant une version haut-débit de la méthode d'immunoprécipitation de la chromatine (ChIP), appelée ChIP-seq. Nous avons suivi la mono-méthylation de la lysine K20 sur l'histone H4 et la tri-méthylation de la lysine K27 sur l'histone H3, marqueurs respectifs de la chromatine ouverte et fermée. En accord avec les changements de niveaux d'expression observés pour de multiples gènes tout le long des chromosomes affectés par les CNVs, nous avons aussi détecté des régions présentant des modifications d'histones entre les échantillons, situées de part et d'autre des régions critiques, jusqu'aux extrémités du chromosome réarrangé. Nous avons aussi évalué les interactions intra-chromosomiques ayant lieu dans ces cellules par l'utilisation de la technique de capture de conformation des chromosomes (4C-seq). Nous avons observé qu'un groupe de gènes flanquants la région critique du syndrome de Williams-Beuren (WBSCR) forment souvent une boucle, constituant un groupe d'interactions privilégiées entre ces gènes et la WBSCR. La délétion de la WBSCR perturbe l'expression de ce groupe de gènes flanquants, mais également les interactions à grande échelle entre eux et la région réarrangée. Nous en concluons que les larges réarrangements génomiques peuvent aboutir à des changements de l'état de la chromatine pouvant s'étendre bien plus loin que la région critique, affectant donc potentiellement l'expression de manière globale et ainsi modifiant le phénotype des patients.

Anti-leishmanial and structure-activity relationship of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives

A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E)-3-(3,4,5-trimethoxy-phenyl)-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl)-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.

Population structure and diversity of the pathogenic fungus Aspergillus fumigatus isolated from different sources and geographic origins

Fifty-five clinical and environmental Aspergillus fumigatus isolates from Mexico, Argentina, France and Peru were analyzed to determine their genetic variability, reproductive system and level of differentiation using amplified fragment length polymorphism markers. The level of genetic variability was assessed by measuring the percentage of polymorphic loci, number of effective alleles, expected heterozygocity and by performing an association index test (I A). The degree of genetic differentiation and variation was determined using analysis of molecular variance at three levels. Using the paired genetic distances, a dendrogram was built to detect the genetic relationship among alleles. Finally, a network of haplotypes was constructed to determine the geographic relationship among them. The results indicate that the clinical isolates have greater genetic variability than the environmental isolates. The I A of the clinical and environmental isolates suggests a recombining population structure. The genetic differentiation among isolates and the dendrogram suggest that the groups of isolates are different. The network of haplotypes demonstrates that the majority of the isolates are grouped according to geographic origin.

Phylogenetic plant community structure along elevation is lineage specific

The trend of closely related taxa to retain similar environmental preferences mediated by inherited traits suggests that several patterns observed at the community scale originate from longer evolutionary processes. While the effects of phylogenetic relatedness have been previously studied within a single genus or family, lineage-specific effects on the ecological processes governing community assembly have rarely been studied for entire communities or flora. Here, we measured how community phylogenetic structure varies across a wide elevation gradient for plant lineages represented by thirty-five families, using a co-occurrence index and net relatedness index (NRI). We propose a framework that analyses each lineage separately and reveals the trend of ecological assembly at tree nodes. We found prevailing phylogenetic clustering for more ancient nodes and overdispersion in more recent tree nodes. Closely related species may thus rapidly evolve new environmental tolerances to radiate into distinct communities, while older lineages likely retain inherent environmental tolerances to occupy communities in similar environments, either through efficient dispersal mechanisms or the exclusion of older lineages with more divergent environmental tolerances. Our study illustrates the importance of disentangling the patterns of community assembly among lineages to better interpret the ecological role of traits. It also sheds light on studies reporting absence of phylogenetic signal, and opens new perspectives on the analysis of niche and trait conservatism across lineages.