P-element distribution in Eurasian populations of Drosophila melanogaster: A genetic and molecular analysis

Genetic and molecular investigations were carried out with Eurasian Drosophila melanogaster populations on the P-M system of hybrid dysgenesis. In 27 strains sampled from France to Middle Asia, a clear gradient exists between Western Europe, in which most modern strains are of the Q type, and eastern areas, in which M-cytotype strains predominate. Molecular analysis on individual flies was performed with two complementary probes of the cloned 2.9-kilobase P element. The results provide evidence for a gradually decreasing frequency of P elements from west to east, but the presence of P-homologous sequences has been ascertained in all of the wild M-cytotype populations analyzed. Moreover, some active P elements with GD sterility potential were revealed in the majority of M-cytotype populations when tested with a highly sensitive reference line. The gradual change in distribution of the polymorphic P family in Eurasia is discussed in relation to the structure of the elements together with the theories of P-M evolution and is interpreted as the present invasion of Eurasian populations by these elements.     

Complexities in the genetic structure of Anopheles gambiae populations in west Africa as revealed by microsatellite DNA analysis

Chromosomal forms of Anopheles gambiae, given the informal designations Bamako, Mopti, and Savannah, have been recognized by the presence or absence of four paracentric inversions on chromosome 2. Studies of karyotype frequencies at sites where the forms occur in sympatry have led to the suggestion that these forms represent species. We conducted a study of the genetic structure of populations of An. gambiae from two villages in Mali, west Africa. Populations at each site were composed of the Bamako and Mopti forms and the sibling species, Anopheles arabiensis. Karyotypes were determined for each individual mosquito and genotypes at 21 microsatellite loci determined. A number of the microsatellites have been physically mapped to polytene chromosomes, making it possible to select loci based on their position relative to the inversions used to define forms. We found that the chromosomal forms differ at all loci on chromosome 2, but there were few differences for loci on other chromosomes. Geographic variation was small. Gene flow appears to vary among different regions within the genome, being lowest on chromosome 2, probably due to hitchhiking with the inversions. We conclude that the majority of observed genetic divergence between chromosomal forms can be explained by forces that need not involve reproductive isolation, although reproductive isolation is not ruled out. We found low levels of gene flow between the sibling species Anopheles gambiae and Anopheles arabiensis, similar to estimates based on observed frequencies of hybrid karyotypes in natural populations.     

Genetic Structure Inferred from Mitochondrial 12S Ribosomal RNA Sequence of Oncomelania quadrasi,the Intermediate Snail Host of Schistosoma japonicum in the Philippines

Species and subspecies of the Oncomelania hupensis species complex are recognized as intermediate hosts of Schistosoma japonicum. Of these species and subspecies, O. quadrasi is distributed throughout the Philippines. This study used 12S ribosomal RNA sequences to explore the genetic structure of O. quadrasi populations in the Philippines. Three subspecies, O. h. hupensis, O. h. formosana, and O. h. chiui of this group were also examined. The phylogenetic tree and haplotypes network showed that O. quadrasi separated from the subspecies. Ten O. quadrasi haplotypes (Oq1–Oq10) clustered in relation to their geographic origin. Genetic differentiation (F_ST) and estimated gene flow (Nm) among populations showed significant differences, ranging from 0.556–1.000 to 0.00–0.74, respectively. Genetic differences among groups (F_CT = 0.466), populations within a group (F_SC = 0.727), and populations (F_ST = 0.854) were observed. These results indicate that the O. quadrasi populations in the Philippines have a substructure associated with their geographic origin.     

Phylogenetic incongruence arising from fragmented speciation in enteric bacteria

Evolutionary relationships among species are often assumed to be fundamentally unambiguous, where genes within a genome are thought to evolve in concert and phylogenetic incongruence between individual orthologs is attributed to idiosyncrasies in their evolution. We have identified substantial incongruence between the phylogenies of orthologous genes in Escherichia, Salmonella, and Citrobacter, or E. coli, E. fergusonii, and E. albertii. The source of incongruence was inferred to be recombination, because individual genes support conflicting topology more robustly than expected from stochastic sequence homoplasies. Clustering of phylogenetically informative sites on the genome indicated that the regions of recombination extended over several kilobases. Analysis of phylogenetically distant taxa resulted in consensus among individual gene phylogenies, suggesting that recombination is not ongoing; instead, conflicting relationships among genes in descendent taxa reflect recombination among their ancestors. Incongruence could have resulted from random assortment of ancestral polymorphisms if species were instantly created from the division of a recombining population. However, the estimated branch lengths in alternative phylogenies would require ancestral populations with far more diversity than is found in extant populations. Rather, these and previous data collectively suggest that genome-wide recombination rates decreased gradually, with variation in rate among loci, leading to pluralistic relationships among their descendent taxa.     

Dominance and the evolutionary accumulation of cis- and trans-effects on gene expression

Gene expression levels appear to be under pervasive stabilizing selection. Yet the genetic architecture underlying abundant gene expression diversity within and between populations remains elusive. Here, we investigated the role of dominance in the segregation of cis- and trans-regulation within and between populations. We used chromosome substitution lines of Drosophila melanogaster to show that (i) >70% of the genes that are differentially expressed between two homozygous lines are masked in the heterozygous, suggesting that one of the substituted chromosomes contains a recessive allele; (ii) such large masking is already obtained with heterozygous chromosomes originating from the same population, with the time of divergence between chromosomes in heterozygous lines making only a small but significant contribution to the masking of variation observed in homozygous lines; (iii) variation in gene expression due to trans-regulation is biased toward greater deviations from additivity because of recessive and dominant alleles, whereas variation due to cis-regulation shows higher additivity; and (iv) genetic divergence between second chromosomes is associated with increased cis-regulation, whereas the level of trans-regulation shows little increase over the time scale studied. Our results indicate that cis-acting alleles may be preferentially fixed by positive natural selection because of their higher additivity, and that the disruption of gene expression by recessive variation with pervasive trans-effects may be important for understanding gene expression variation within populations. We suggest that widespread regulatory effects of recessive low-frequency homozygous variation may provide a general mechanism mediating disease phenotypes and the genetic load of natural populations.     

Evolutionary ecology of pungency in wild chilies

The primary function of fruit is to attract animals that disperse viable seeds, but the nutritional rewards that attract beneficial consumers also attract consumers that kill seeds instead of dispersing them. Many of these unwanted consumers are microbes, and microbial defense is commonly invoked to explain the bitter, distasteful, occasionally toxic chemicals found in many ripe fruits. This explanation has been criticized, however, due to a lack of evidence that microbial consumers influence fruit chemistry in wild populations. In the present study, we use wild chilies to show that chemical defense of ripe fruit reflects variation in the risk of microbial attack. Capsaicinoids are the chemicals responsible for the well known pungency of chili fruits. Capsicum chacoense is naturally polymorphic for the production of capsaicinoids and displays geographic variation in the proportion of individual plants in a population that produce capsaicinoids. We show that this variation is directly linked to variation in the damage caused by a fungal pathogen of chili seeds. We find that Fusarium fungus is the primary cause of predispersal chili seed mortality, and we experimentally demonstrate that capsaicinoids protect chili seeds from Fusarium. Further, foraging by hemipteran insects facilitates the entry of Fusarium into fruits, and we show that variation in hemipteran foraging pressure among chili populations predicts the proportion of plants in a population producing capsaicinoids. These results suggest that the pungency in chilies may be an adaptive response to selection by a microbial pathogen, supporting the influence of microbial consumers on fruit chemistry.     

Changed gene expression for candidate ageing genes in long-lived Bicyclus anynana butterflies

Candidate genes for the regulation of lifespan have emerged from studies that use mutants and genetically manipulated model organisms. However, it is rarely addressed whether these genes contribute to lifespan variation in populations of these species that capture natural standing genetic variation. Here, we explore expression variation in three candidate ageing genes, Indy, sod2, and catalase, in Bicyclus anynana, a butterfly with well understood ecology.We used lines established from natural populations and artificially selected for increased adult starvation resistance. They show a considerable increase in adult lifespan under both starvation and optimal food conditions. We measured adult butterflies of various ages, under a range of optimal and starvation diets, from two selected populations and one unselected control population.In all lines, Indy and catalase are up-regulated in response to starvation while this is not evident for sod2. Under starvation, Indy and catalase are up-regulated in, while this is not evident for sod2. Under optimal food conditions, Indy is down-regulated at a later age, with Indy expression showing relatively high inter-individual variation. We find differences between the selected lines and the unselected line. Under starvation conditions, expression is higher for catalase in one, and for sod2 in both selected lines. Importantly, sod2 expression is also higher in the selected populations under optimal food conditions.We conclude that sod2, but not Indy, is involved in the response to artificial selection for increased starvation resistance. The role of catalase is less clear because of the differences between the two selected lines. Moreover, sod2 appears to be a candidate gene that underpins the genetic correlation between starvation resistance and longevity. Our study indicates that some, but not all, genes identified through mutant screens in other organisms may underpin standing genetic variation for ageing-related traits in stocks of Bicyclus butterflies established from natural populations. Clearly, this needs to be investigated in other organisms as well, especially in the organisms to which mutants screens were applied. This information will narrow down the list of genes that underpin variation in lifespan and ageing in extant populations of organisms, and which may serve as candidate genes in humans.     

Heterogeneous selection on exploration behavior within and among West European populations of a passerine bird

Heterogeneous selection is often proposed as a key mechanism maintaining repeatable behavioral variation (“animal personality”) in wild populations. Previous studies largely focused on temporal variation in selection within single populations. The relative importance of spatial versus temporal variation remains unexplored, despite these processes having distinct effects on local adaptation. Using data from >3,500 great tits (Parus major) and 35 nest box plots situated within five West-European populations monitored over 4 to 18 y, we show that selection on exploration behavior varies primarily spatially, across populations, and study plots within populations. Exploration was, simultaneously, selectively neutral in the average population and year. These findings imply that spatial variation in selection may represent a primary mechanism maintaining animal personalities, likely promoting the evolution of local adaptation, phenotype-dependent dispersal, and nonrandom settlement. Selection also varied within populations among years, which may counteract local adaptation. Our study underlines the importance of combining multiple spatiotemporal scales in the study of behavioral adaptation.

Repeatable and heritable variation in behavior (“animal personality”) is ubiquitous among wild animal populations (1). Repeatable behavioral differences among individuals can be adaptive when the costs and benefits of alternative behavioral tactics vary with the environment (2, 3). This requires heterogeneous selection, either spatially, temporally, or spatiotemporally (e.g., within or among populations, habitats, or years) (3, 4). Social environments may also play a key role by inducing negative frequency-dependent selection (5, 6). Heterogeneous selection on repeatable individual variation in behavior has previously been demonstrated primarily within single populations sampled over limited numbers of years (7, 8), thus limiting our understanding of the relative importance of spatial and temporal variation in selection.Spatial and temporal processes co-occur (8, 9) but have distinct effects on population dynamics and evolution. Strong spatial variation favors different behavioral phenotypes in different locations, which may induce selection for nonrandom dispersal and rapid population divergence (10, 11). Temporal variation instead favors the coexistence of multiple behavioral phenotypes within populations, thereby counteracting population divergence. Estimates of selection from multiple study populations monitored over multiple years are required to estimate spatial and temporal variation simultaneously and determine their relative importance in maintaining individual behavioral variation.To address this question, we assayed exploration behavior in a novel environment (12) among great tits (Parus major) breeding in 35 nest box plots across five populations in Western Europe, each sampled for multiple (4 to 18) years. For four of these populations, animal model–based quantitative genetics were conducted; in all cases, exploration behavior was significantly repeatable and heritable [Boshoek, Belgium: R = 0.42, h² = 0.30 (13, 14); Lauwersmeer, the Netherlands: R = 0.40 to 0.44, h² = 0.10 to 0.11 (13, 15); Westerheide, the Netherlands: R = 0.38, h² = 0.14 (13, 16); Wytham Woods, United Kingdom: R = 0.34, h² = 0.26 (13, 16)]. We estimated the average pattern of selection (directional, stabilizing, disruptive) within the average population, plot, and year and examined whether selection was heterogeneous as predicted by state-dependent personality models (3, 4). Finally, we estimated the relative proportion of variation in selection that was attributable to five distinct sources: 1) macrospatial variation (among populations), 2) microspatial variation (among plots within populations), 3) temporal variation (among years), 4) population-specific (or macroscale) temporal variation (unique combinations of population and year), and 5) plot-specific (or microscale) temporal variation (unique combinations of plot and year) (Fig. 1).Open in a separate windowFig. 1.Distinct heterogeneous selection scenarios illustrated for two populations with two plots each sampled over the same two years. Selection can vary (A) macrospatially (among populations), (B) microspatially (among plots), (C) temporally (among years), (D) macrospatiotemporally (year effects are population specific), and (E) microspatiotemporally (year effects are plot specific). Illustrated scenarios are mutually nonexclusive; our analyses of the sources of variation in selection on exploration behavior imply all mechanisms are important.     

Evolution of hybrid dysgenesis determinants in Drosophila melanogaster

Hybrid dysgenesis is manifested as a group of correlated aberrant genetic traits such as sterility, increased mutation rate, and male recombination. Previous work has shown that it appears when males of strains carrying either of two independent families of transposable elements called I and P factors are hybridized with females of susceptible strains called R and M, respectively. Here the results of an extensive survey for dysgenic potential in Drosophila melanogaster strains are reported. Striking temporal trends in the distribution of strains were observed with respect to the two transposable element systems; in particular, the frequency of R and M strains is positively correlated with laboratory age. In recent tests of strain samples, those collected from nature about 50 years ago were the earliest observed to possess I characteristics. The I type was increasingly frequent in samples from strains more recently originating in the wild. This type is apparently ubiquitous in present day natural populations. the P type was not found in strain samples collected before 1950, and collections made subsequently showed increasing frequencies of P-factor activity with decreasing laboratory age. Marked geographical patterns are documented in the contemporary worldwide distribution of variant strains within the P-M system. M strains are currently fairly common in natural populations from various parts of the world, except on the American continent where they are rare. The degree and distribution of quantitative variation within M and P strain categories is related to their time of origin in the wild. The implications of these results are discussed in relation to the hypothesis that hybrid dysgenesis determinants have evolved recently in natural populations and to an alternative hypothesis of laboratory evolution.     

Assessment of the contamination potentials of some foodborne bacteria in biofilms for food products

ObjectiveTo assess biofilms formed by different bacterial strains on glass slides, and changes in biofilm mass and biofilm-associated cell populations after brief contacts between biofilms and either media agar or food products.MethodsTwo Listeria monocytogenes and Escherichia coli (E. coli) strains and a single Staphylococcus aureus (S. aureus) strain were inoculated separately in tryptic soy broth containing glass coupons incubated for 24, 48 or 72 h at 37 °C. The biofilms formed by individual bacterial strains and biofilm-associated cell populations were determined. Biofilms were subsequently allowed to have brief contacts (1-3 times), through gentle touching, with either agar, meat or soft white cheese (2 cm³). Changes in biofilm mass on glass slides and cell populations embedded in biofilms were quantified.ResultsA nonpathogenic E. coli formed more biofilms than an E. coli O157:H7 strain. Biofilms formed by S. aureus and Listeria monocytogenes were essentially similar. The biofilm mass increased as incubation time increased within 48 h of incubation and was not positively correlated with cellulose production. Biofilm mass at 48 and 72 h of incubation was not significantly different. More frequent contacts with agar or foods did not remove more biofilms or biofilm-associated cells from glass slides. More S. aureus biofilms were removed followed by Listeria and E. coli biofilms. Mean contamination of agar or food models was 0.00 to 7.65 log CFU/cm². Greater contaminations in cell populations were observed with S. aureus and Listeria biofilms.ConclusionsThe results provide a clearer assessment of contaminating potential of foods that comes in contact with them.     

Changes related to gender,geographic population and habitat in the antennal phenotype of Triatoma patagonica Del Ponte, 1929 (Hemiptera: Reduviidae)

Triatomines undergo morphological changes as an adaptive response to different habitats (wild, peridomestic, domestic, laboratory). The characterization of the antennal phenotype provides information on intraspecific variation caused by geographical origin and/or habitat. Triatoma patagonica Del Ponte, 1929 is known to occur in peridomiciles of rural areas in Argentina, where it also invades non-colonized dwellings. Here we describe and compare the antennal phenotype of T. patagonica in populations of different geographic origin, and explore possible modifications induced by laboratory rearing with the aim of investigating the range of phenotypic variation of the species for the first time. Sixty antennas of adult males and females of T. patagonica belonging to two peridomiciliary populations of different geographical origin were analyzed. Four types of sensilla were observed in three antennal segments, showing sexual dimorphism in the species. The multivariate analysis separated the populations of similar habitat (peridomicile) but different geographical origin, without showing differences between the peridomiciliary and laboratory populations of the same geographical origin. These results suggest phenotypic plasticity in T. patagonica, which would allow the species to adapt to a wide range of habitats without having a close association with a given host and its environment. The range of antennal phenotypic variation of T. patagonica would also be an indicator of its current stage of adaptation to the human environment.     

Dietary patterns and fatty acids levels of three European populations. Results from the IMMIDIET study

Background and aimsDifferences in blood fatty acids (FAs) profile among populations with different lifestyle have partly been attributed to differences in food intake. A holistic approach in dietary guidance through dietary patterns is essential. This study aimed at evaluating the main plasma and red blood cell (RBC) FAs in three European populations and assessing the role of dietary patterns in explaining variation in their levels.MethodsIn the framework of the IMMIDIET Project, 1604 subjects (802 male–female pairs) aged 26–65 years were enrolled in Italy, Belgium and UK. Plasma and RBC FAs were measured. One year recall food frequency questionnaires were used to evaluate dietary habits of each individual.ResultsItalian cohort showed lower plasma and RBC n − 3 levels than participants of the other two populations (P < 0.001). Both plasma and RBC arachidonic acid were higher in Italian cohort as compared to Belgian and English. Reduced rank regression analysis indicated two dietary patterns explaining 35% and 17% of the total variation of the sum of plasma and RBC n − 3, respectively. In a holistic dietary analysis, neither fish nor mollusks intake seemed to contribute to n − 3 variation as compared to vegetable oils and polyphenol-rich foods.ConclusionThe Italian cohort presented significant lower plasma and RBC n − 3 FA levels compared to Belgians and English. A holistic approach in dietary analysis seemed to explain a relatively high proportion of plasma and RBC n − 3 FAs variability. Dietary pattern analysis may contribute to the study of the association of human diet with FAs levels.     

应用mtDNA-COⅠ基因序列研究我国大劣按蚊A、D群体的遗传差异

目的 应用线粒体DNA细胞色素氧化酶亚单位Ⅰ（mtDNA-COⅠ）基因序列特征阐明我国大劣按蚊A、D群体的遗传差异和分化水平。 方法 研究样本包括大劣按蚊A海南群体（n=13）,大劣按蚊D云南江城群体（n=17）和勐腊群体（n=17）,所有样本均以rDNA-ITS2序列差异为依据,进行分子鉴别确认;扩增和测定mtDNA-COⅠ基因片段,用MEGA（Version2.1）、TCS（Version1.12）、ARLEQUIN（Version2.0）等软件对基因序列进行生物信息学分析。 结果 分析mtDNA-COⅠ基因中长度为959 bp的片段,显示大劣按蚊A的单倍型共3个,大劣按蚊D的单倍型共6个,均匀分布于3个群体。勐腊群体内错配平均数（7.441 2）明显大于江城群体（1.279 4）和海南群体（1.051 3）,表明勐腊群体内个体间分化程度最大。分步AMOVA的计算结果显示群体间基因交流有限（Fst＝0.799 9）,群体间变异（79.99%）明显大于群体内变异（20.01%）。 结论 我国大劣按蚊A、D群体之间的遗传差异较小,个体间的分化水平较高。     

Investigation of Biological Factors Contributing to Individual Variation in Viral Titer after Oral Infection of Aedes aegypti Mosquitoes by Sindbis Virus

The mechanisms involved in determining arbovirus vector competence, or the ability of an arbovirus to infect and be transmitted by an arthropod vector, are still incompletely understood. It is well known that vector competence for a particular arbovirus can vary widely among different populations of a mosquito species, which is generally attributed to genetic differences between populations. What is less understood is the considerable variability (up to several logs) that is routinely observed in the virus titer between individual mosquitoes in a single experiment, even in mosquitoes from highly inbred lines. This extreme degree of variation in the virus titer between individual mosquitoes has been largely ignored in past studies. We investigated which biological factors can affect titer variation between individual mosquitoes of a laboratory strain of Aedes aegypti, the Orlando strain, after Sindbis virus infection. Greater titer variation was observed after oral versus intrathoracic infection, suggesting that the midgut barrier contributes to titer variability. Among the other factors tested, only the length of the incubation period affected the degree of titer variability, while virus strain, mosquito strain, mosquito age, mosquito weight, amount of blood ingested, and virus concentration in the blood meal had no discernible effect. We also observed differences in culture adaptability and in the ability to orally infect mosquitoes between virus populations obtained from low and high titer mosquitoes, suggesting that founder effects may affect the virus titer in individual mosquitoes, although other explanations also remain possible.     

Polygenic and directional regulatory evolution across pathways in Saccharomyces

The search to understand how genomes innovate in response to selection dominates the field of evolutionary biology. Powerful molecular evolution approaches have been developed to test individual loci for signatures of selection. In many cases, however, an organism''s response to changes in selective pressure may be mediated by multiple genes, whose products function together in a cellular process or pathway. Here we assess the prevalence of polygenic evolution in pathways in the yeasts Saccharomyces cerevisiae and S. bayanus. We first established short-read sequencing methods to detect cis-regulatory variation in a diploid hybrid between the species. We then tested for the scenario in which selective pressure in one species to increase or decrease the activity of a pathway has driven the accumulation of cis-regulatory variants that act in the same direction on gene expression. Application of this test revealed a variety of yeast pathways with evidence for directional regulatory evolution. In parallel, we also used population genomic sequencing data to compare protein and cis-regulatory variation within and between species. We identified pathways with evidence for divergence within S. cerevisiae, and we detected signatures of positive selection between S. cerevisiae and S. bayanus. Our results point to polygenic, pathway-level change as a common evolutionary mechanism among yeasts. We suggest that pathway analyses, including our test for directional regulatory evolution, will prove to be a relevant and powerful strategy in many evolutionary genomic applications.     

Quantitative genetic variation of enzyme activities in natural populations of Drosophila melanogaster

The genetic component of variation of enzyme activity in natural populations of Drosophila melanogaster was investigated by using two sets of chromosome substitution lines. The constitution of a line of each type is: i₁/i₁;+₂/ +₂;i₃/i₃ and i₁/i₁;i₂/ i₂;+₃/+₃, where i refers to a chromosome from a highly inbred line and + refers to a chromosome from a natural population. The + but not the i chromosomes vary within a set of lines. By use of a randomized block design to test and estimate components of variance, 50 of the second- and 50 of the third- chromosome substitution lines have been screened for variation in the activity levels of seven enzymes. Six of the seven enzymes show a significant genetic component in at least one set of lines, and five of the seven enzymes show activity variations attributable to factors that are not linked to the structural gene. These unlinked activity modifiers identify possible regulatory elements. Analyses of covariance show that most of the genetic variation of enzyme activities cannot be accounted for by genetic variation of live weight or protein content. These results and the lack of strong correlations between the genetic effects on the activities of different enzymes indicate that the effects are mainly specific for individual enzymes.     

Conventional parasitology and DNA-based diagnostic methods for onchocerciasis elimination programmes

Commonly used methods for diagnosing Onchocerca volvulus infections (microscopic detection of microfilariae in skin snips and nodule palpation) are insensitive. Improved methods are needed for monitoring and evaluation of onchocerciasis elimination programmes and for clinical diagnosis of individual patients. A sensitive probe-based qPCR assay was developed for detecting O. volvulus DNA, and this was tested with samples collected from an endemic area in eastern Côte d’Ivoire. The new test was evaluated with dried skin snip pairs from 369 subjects and compared to routine skin snip microscopy and nodule palpation results from the same individuals. Onchocerciasis prevalence for these samples by qPCR, skin snip microscopy, and nodule palpation were 56.9%, 26.0%, and 37.9%, respectively. Furthermore, the combination of all three tests produced an infection prevalence of 72.9%, which was significantly higher than 53.1% detected by microscopy plus nodule palpation without qPCR. However, the qPCR assay was negative for 54 of 229 individuals with palpable nodules. qPCR could be a useful tool for detecting residual O. volvulus infections in human populations as prevalence decreases in areas following community-directed treatment with ivermectin.     

Hybrid therapy for Helicobacter pylori infection: A systemic review and meta-analysis

AIM: To compare the effectiveness of hybrid therapy with other recommended regimens using meta-analysis.METHODS: Bibliographical searches for randomized trials comparing hybrid and other therapies were performed in PubMed, the Cochrane Library and relevant congresses up to February 2015 using the following keywords (all fields and/or MeSH): (“Helicobacter pylori” or “H. pylori”) and (“hybrid therapy” or “sequential-concomitant therapy”). Meta-analyses were performed with Cochrane Review Manager 5.1. The random effect model proposed by DerSimonian and Laird and the Mantel-Haenszel method were used to estimate the pooled relative risk and 95%CI of the efficacy outcomes between hybrid therapy and other eradication therapies.RESULTS: Eight studies (2516 subjects) met entry criteria. The antimicrobial resistance in the study groups ranged from 6.9% to 23.5%. The mean cure rates of hybrid therapy by intention-to-treat (ITT) and per-protocol analyses were 88.5% (n = 1207; range: 80.0% to 97.4%) and 93.3% (n = 1109; range: 85.7% to 99.1%), respectively. Meta-analysis showed there was no significant difference in ITT eradication rate between hybrid and sequential therapy (relative risk: 1.01; 95%CI: 0.92-1.11). Subgroup analysis revealed hybrid therapy was more effective than sequential therapy in the non-Italian populations (95%CI: 1.01-1.18) and was only less effective in one, Italian population (95%CI: 0.83-0.98). There was no significant difference in eradication rate between hybrid therapy and concomitant therapy (95%CI: 0.93-1.02). No head-to-head comparisons of hybrid therapy and standard triple therapy or bismuth quadruple therapy were found. However, a multicenter, randomized trial showed that reverse hybrid therapy was superior to standard triple therapy (95.5% vs 88.6% ITT; P = 0.011).CONCLUSION: Hybrid therapy appears to be an effective, safe, and well-tolerated treatment for H. pylori infection in the era of increasing antibiotic resistance.     

Genome-wide patterns of population structure and admixture in West Africans and African Americans

Quantifying patterns of population structure in Africans and African Americans illuminates the history of human populations and is critical for undertaking medical genomic studies on a global scale. To obtain a fine-scale genome-wide perspective of ancestry, we analyze Affymetrix GeneChip 500K genotype data from African Americans (n = 365) and individuals with ancestry from West Africa (n = 203 from 12 populations) and Europe (n = 400 from 42 countries). We find that population structure within the West African sample reflects primarily language and secondarily geographical distance, echoing the Bantu expansion. Among African Americans, analysis of genomic admixture by a principal component-based approach indicates that the median proportion of European ancestry is 18.5% (25th–75th percentiles: 11.6–27.7%), with very large variation among individuals. In the African-American sample as a whole, few autosomal regions showed exceptionally high or low mean African ancestry, but the X chromosome showed elevated levels of African ancestry, consistent with a sex-biased pattern of gene flow with an excess of European male and African female ancestry. We also find that genomic profiles of individual African Americans afford personalized ancestry reconstructions differentiating ancient vs. recent European and African ancestry. Finally, patterns of genetic similarity among inferred African segments of African-American genomes and genomes of contemporary African populations included in this study suggest African ancestry is most similar to non-Bantu Niger-Kordofanian-speaking populations, consistent with historical documents of the African Diaspora and trans-Atlantic slave trade.     

Association of Genetic Variation with Gene Expression and Protein Abundance within the Natriuretic Peptide Pathway

The natriuretic peptide (NP) system is a critical physiologic pathway in heart failure with wide individual variability in functioning. We investigated the genetic component by testing the association of single nucleotide polymorphisms (SNP) with RNA and protein expression. Samples of DNA, RNA, and tissue from human kidney (n?=?103) underwent genotyping, RT-PCR, and protein quantitation (in lysates), for four candidate genes [NP receptor 1 (NPR1), NPR2, and NPR3 and membrane metalloendopeptidase]. The association of genetic variation with expression was tested using linear regression for individual SNPs, and a principal components (PC) method for overall gene variation. Eleven SNPs in NPR2 were significantly associated with protein expression (false discovery rate ≤0.05), but not RNA quantity. RNA and protein quantity correlated poorly with each other. The PC analysis showed only NPR2 as significant. Assessment of the clinical impact of NPR2 genetic variation is needed.