Spatial and temporal variation in population genetic structure of wild Nile tilapia (Oreochromis niloticus) across Africa

Background: Reconstructing the evolutionary history of a species is challenging. It often depends not only on the past biogeographic and climatic events but also the contemporary and ecological factors, such as current connectivity and habitat heterogeneity. In fact, these factors might interact with each other and shape the current species distribution. However, to what extent the current population genetic structure reflects the past and the contemporary factors is largely unknown. Here we investigated spatio-temporal genetic structures of Nile tilapia (Oreochromis niloticus) populations, across their natural distribution in Africa. While its large biogeographic distribution can cause genetic differentiation at the paleo-biogeographic scales, its restricted dispersal capacity might induce a strong genetic structure at micro-geographic scales. Results: Using nine microsatellite loci and 350 samples from ten natural populations, we found the highest genetic differentiation among the three ichthyofaunal provinces and regions (Ethiopian, Nilotic and Sudano-Sahelian) (R(ST) = 0.38 - 0.69). This result suggests the predominant effect of paleo-geographic events at macro-geographic scale. In addition, intermediate divergences were found between rivers and lakes within the regions, presumably reflecting relatively recent interruptions of gene flow between hydrographic basins (R(ST) = 0.24 - 0.32). The lowest differentiations were observed among connected populations within a basin (R(ST) = 0.015 in the Volta basin). Comparison of temporal sample series revealed subtle changes in the gene pools in a few generations (F = 0 - 0.053). The estimated effective population sizes were 23 - 143 and the estimated migration rate was moderate (m similar to 0.094 - 0.097) in the Volta populations. Conclusions: This study revealed clear hierarchical patterns of the population genetic structuring of O. niloticus in Africa. The effects of paleo-geographic and climatic events were predominant at macro-geographic scale, and the significant effect of geographic connectivity was detected at micro-geographic scale. The estimated effective population size, the moderate level of dispersal and the rapid temporal change in genetic composition might reflect a potential effect of life history strategy on population dynamics. This hypothesis deserves further investigation. The dynamic pattern revealed at micro-geographic and temporal scales appears important from a genetic resource management as well as from a biodiversity conservation point of view.

Species-Specific Relationships between Water Transparency and Male Coloration within and between Two Closely Related Lake Victoria Cichlid Species

Environmental variation in signalling conditions affects animal communication traits, with possible consequences for sexual selection and reproductive isolation. Using spectrophotometry, we studied how male coloration within and between populations of two closely related Lake Victoria cichlid species (Pundamilia pundamilia and P. nyererei) covaries with water transparency. Focusing on coloration patches implicated in sexual selection, we predicted that in clear waters, with broad-spectrum light, (1) colours should become more saturated and (2) shift in hue away from the dominant ambient wavelengths, compared to more turbid waters. We found support for these predictions for the red and yellow coloration of P. nyererei but not the blue coloration of P. pundamilia. This may be explained by the species difference in depth distribution, which generates a steeper gradient in visual conditions for P. nyererei compared to P. pundamilia. Alternatively, the importance of male coloration in intraspecific sexual selection may differ between the species. We also found that anal fin spots, that is, the orange spots on male haplochromine anal fins that presumably mimic eggs, covaried with water transparency in a similar way for both species. This is in contrast to the other body regions studied and suggests that, while indeed functioning as signals, these spots may not play a role in species differentiation.

Prediction of whole-genome DNA-DNA similarity, determination of G+C content and phylogenetic analysis within the family Pasteurellaceae by multilocus sequence analysis (MLSA)

Genome predictions based on selected genes would be a very welcome approach for taxonomic studies, including DNA-DNA similarity, G+C content and representative phylogeny of bacteria. At present, DNA-DNA hybridizations are still considered the gold standard in species descriptions. However, this method is time-consuming and troublesome, and datasets can vary significantly between experiments as well as between laboratories. For the same reasons, full matrix hybridizations are rarely performed, weakening the significance of the results obtained. The authors established a universal sequencing approach for the three genes recN, rpoA and thdF for the Pasteurellaceae, and determined if the sequences could be used for predicting DNA-DNA relatedness within the family. The sequence-based similarity values calculated using a previously published formula proved most useful for species and genus separation, indicating that this method provides better resolution and no experimental variation compared to hybridization. By this method, cross-comparisons within the family over species and genus borders easily become possible. The three genes also serve as an indicator of the genome G+C content of a species. A mean divergence of around 1 % was observed from the classical method, which in itself has poor reproducibility. Finally, the three genes can be used alone or in combination with already-established 16S rRNA, rpoB and infB gene-sequencing strategies in a multisequence-based phylogeny for the family Pasteurellaceae. It is proposed to use the three sequences as a taxonomic tool, replacing DNA-DNA hybridization.

Expression and diversity of Echinococcus multilocularis AgB genes in secondarily infected mice: evaluating the influence of T-cell immune selection on antigenic variation

The T-cell-mediated immune response exhibits a crucial function in the control of the intrahepatic proliferation of Echinococcus multilocularis larvae in mice and humans, both being natural intermediate hosts of the parasite. Antigen B (AgB), a metabolized Echinococcus spp. lipoprotein, contributes to the modulation of the T-cell immune response, and distinct sites of the corresponding AgB1, AgB3 and AgB4 genes were shown to be under positive selection pressure. Since several AgB gene variants are present in a single Echinococcus metacestode, we used secondary E. multilocularis infections in BALB/c and in athymic nude mice (devoid of T-cell responses) to analyze the effect of the cellular immune response on the expression and diversity of EmAgB1-EmAgB4 genes. We demonstrated hereby that EmAgB transcripts were less abundant in nude mice during the early phase of infection (at one month post-infection), and that EmAgB2 is simultaneously down-regulated when compared to the other three genes. A negative relationship exists between the level of transcription and diversity of EmAgB genes. Moreover, no excess of non-synonymous substitutions was found among the distinct EmAgB alleles from a single host. Together, these results pointed to the effect of purifying selection, which seemed to eliminate the detrimental AgB variants generated during the development of the metacestode within the peritoneal cavity of its intermediate host.

To look or not to look at threat? Scanpath differences within a group of spider phobics

Predicting the behavior of phobic patients in a confrontational situation is challenging. While avoidance as a major clinical component of phobias suggests that patients orient away from threat, findings based on cognitive paradigms indicate an attentional bias towards threat. Here we present eye movement data from 21 spider phobics and 21 control subjects, based on 3 basic oculomotor tasks and a visual exploration task that included close-up views of spiders. Relative to the control group, patients showed accelerated reflexive saccades in one of the basic oculomotor tasks, while the fear-relevant exploration task evoked a general slowing in their scanning behavior and pronounced oculomotor avoidance. However, this avoidance strongly varied within the patient group and was not associated with the scores from spider avoidance-sensitive questionnaire scales. We suggest that variation of oculomotor avoidance between phobics reflects different strategies of how they cope with threat in confrontational situations.

Seasonal variation in orthopedic health services utilization in Switzerland: the impact of winter sport tourism

BACKGROUND: Climate- or holiday-related seasonality in hospital admission rates is well known for many diseases. However, little research has addressed the impact of tourism on seasonality in admission rates. We therefore investigated the influence of tourism on emergency admission rates in Switzerland, where winter and summer leisure sport activities in large mountain regions can generate orthopedic injuries. METHODS: Using small area analysis, orthopedic hospital service areas (HSAo) were evaluated for seasonality in emergency admission rates. Winter sport areas were defined using guest bed accommodation rate patterns of guest houses and hotels located above 1000 meters altitude that show clear winter and summer peak seasons. Emergency admissions (years 2000-2002, n = 135'460) of local and nonlocal HSAo residents were evaluated. HSAo were grouped according to their area type (regular or winter sport area) and monthly analyses of admission rates were performed. RESULTS: Of HSAo within the defined winter sport areas 70.8% show a seasonal, summer-winter peak hospital admission rate pattern and only 1 HSAo outside the defined winter sport areas shows such a pattern. Seasonal hospital admission rates in HSAo in winter sport areas can be up to 4 times higher in winter than the intermediate seasons, and they are almost entirely due to admissions of nonlocal residents. These nonlocal residents are in general -and especially in winter- younger than local residents, and nonlocal residents have a shorter length of stay in winter sport than in regular areas. The overall geographic distribution of nonlocal residents admitted for emergencies shows highest rates during the winter as well as the summer in the winter sport areas. CONCLUSION: Small area analysis using orthopedic hospital service areas is a reliable method for the evaluation of seasonality in hospital admission rates. In Switzerland, HSAo defined as winter sport areas show a clear seasonal fluctuation in admission rates of only nonlocal residents, whereas HSAo defined as regular, non-winter sport areas do not show such seasonality. We conclude that leisure sport, and especially ski/snowboard tourism demands great flexibility in hospital beds, staff and resource planning in these areas.

Variation of the mechanical properties of PMMA to suit osteoporotic cancellous bone

Poly(methyl methacrylate) (PMMA) is by far the most frequently used bone substitute material for vertebroplasty. However, there are serious complications, such as cement leakage and an increased fracture rate of the adjacent vertebral bodies. The latter may be related to the mechanical properties of the augmented segment within the osteoporotic spine. A possible counter-measure is prophylactic augmentation at additional levels, but this aggravates the risk for the patient. Introduction of pores is a possible method to reduce the inherent high stiffness of PMMA. This study investigates the effect of porosity on the mechanical properties of PMMA bone cement. Different fractions of a highly viscous liquid were mixed into the PMMA during preparation. An open-porous material with adjustable mechanical properties resulted after removal of the aqueous phase. Different radiopacifiers were admixed to investigate their suitability for vertebroplasty. The final material was characterized mechanically by compressive testing, microscopically and radiologically. In addition, the monomer release subsequent to hardening was measured by means of gas chromatography. The Young's modulus in compression could be varied between 2800 +/- 70 MPa and 120 +/- 150 MPa, and the compression ultimate strength between 170 +/- 5 MPa and 8 +/- 9 MPa for aqueous fractions ranging between 0 and 50% of volume. Only a slight decrease of the Young's modulus and small changes of ultimate strength were found when the mixing time was increased. An organic hydrophilic and lipophilic radiopacifier led to a higher Young's modulus of the porous material; however, the ultimate strength was not significantly affected by adding different radiopacifiers to the porous cement. The radiopacity was lost after washing the aqueous phase out of the pores. No separation occurred between the aqueous and the PMMA phase during injection into an open porous ceramic material. The monomer released was found to increase for increasing aqueous fractions, but remained comparable in magnitude to standard PMMA. This study demonstrates that a conventional PMMA can be modified to obtain a range of mechanical properties, including those of osteoporotic bone.

Genetic variation and demographic history of the Haplochromis laparogramma group of Lake Victoria-An analysis based on SINEs and mitochondrial DNA

More than 500 endemic haplochromine cichlid species inhabit Lake Victoria. This striking species diversity is a classical example of recent explosive adaptive radiation thought to have happened within the last similar to 15,000 years. In this study, we examined the population structure and historical demography of 3 pelagic haplochromine cichlid species that resemble in morphology and have similar niche, Haplochromis (Yssichromis) laparogramma, Haplochromis (Y.) pyrrhocephalus, and Haplochromis (Y.) sp. "glaucocephalus". We investigated the sequences of the mitochondrial DNA control region and the insertion patterns of short interspersed elements (SINEs) of 759 individuals. We show that sympatric forms are genetically differentiated in 4 of 6 cases, but we also found apparent weakening of the genetic differentiation in areas with turbid water. We estimated the timings of population expansion and species divergence to coincide with the refilling of the lake at the Pleistocene/Holocene boundary. We also found that estimates can be altered significantly by the choice of the shape of the molecular clock. If we employ the nonlinear clock model of evolutionary rates in which the rates are higher towards the recent, the population expansion was dated at around the event of desiccation of the lake ca. 17,000 YBP. Thus, we succeeded in clarifying the species and population structure of closely related Lake Victoria cichlids and in showing the importance of applying appropriate clock calibrations in elucidating recent evolutionary events. (C) 2009 Elsevier B.V. All rights reserved.

Mapping Individual Variation in Male Mating Preference Space: Multiple Choice in a Color Polymorphic Cichlid Fish

Sexual selection theory largely rests on the assumption that populations contain individual variation in mating preferences and that individuals are consistent in their preferences. However, there are few empirical studies of within-population variation and even fewer have examined individual male mating preferences. Here, we studied a color polymorphic population of the Lake Victoria cichlid fish Neochromis omnicaeruleus, a species in which color morphs are associated with different sex-determining factors. Wild-caught males were tested in three-way choice trials with multiple combinations of different females belonging to the three color morphs. Compositional log-ratio techniques were applied to analyze individual male mating preferences. Large individual variation in consistency, strength, and direction of male mating preferences for female color morphs was found and hierarchical clustering of the compositional data revealed the presence of four distinct preference groups corresponding to the three color morphs in addition to a no-preference class. Consistency of individual male mating preferences was higher in males with strongest preferences. We discuss the implications of these findings for our understanding of the mechanisms underlying polymorphism in mating preferences.

Impact of definitions of loss to follow-up (LTFU) in antiretroviral therapy program evaluation: variation in the definition can have an appreciable impact on estimated proportions of LTFU

OBJECTIVE To examine the impact of different definitions of loss to follow-up (LTFU) on estimates of program outcomes in cohort studies of patients on antiretroviral therapy (ART). STUDY DESIGN AND SETTING We examined the impact of different definitions of LTFU using data from the International Epidemiological Databases to Evaluate AIDS-Southern Africa. The reference approach, Definition A, was compared with five alternative scenarios that differed in eligibility for analysis and the date assigned to the LTFU outcome. Kaplan-Meier estimates of LTFU were calculated up to 2 years after starting ART. RESULTS Estimated cumulative LTFU were 14% and 22% at 12 and 24 months, respectively, using the reference approach. Differences in the proportion LTFU were reported in the alternative scenarios with 12-month estimates of LTFU varying by up to 39% compared with Definition A. Differences were largest when the date assigned to the LTFU outcome was 6 months after the date of last contact and when the site-specific definition of LTFU was used. CONCLUSION Variation in the definitions of LTFU within cohort analyses can have an appreciable impact on estimated proportions of LTFU over 2 years of follow-up. Use of a standardized definition of LTFU is needed to accurately measure program effectiveness and comparability between programs.

Variation of a test's sensitivity and specificity with disease prevalence

BACKGROUND Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. METHODS We used data from 23 meta-analyses, each of which included 10-39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. RESULTS Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. INTERPRETATION The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation.

Origins of Shared Genetic Variation in African Cichlids

Cichlid fishes have evolved tremendous morphological and behavioral diversity in the waters of East Africa. Within each of the Great Lakes Tanganyika, Malawi, and Victoria, the phenomena of hybridization and retention of ancestral polymorphism explain allele sharing across species. Here, we explore the sharing of single nucleotide polymorphisms (SNPs) between the major East African cichlid assemblages. A set of approximately 200 genic and nongenic SNPs was ascertained in five Lake Malawi species and genotyped in a diverse collection of 160 species from across Africa. We observed segregating polymorphism outside of the Malawi lineage for more than 50% of these loci; this holds similarly for genic versus nongenic SNPs, as well as for SNPs at putative CpG versus non-CpG sites. Bayesian and principal component analyses of genetic structure in the data demonstrate that the Lake Malawi endemic flock is not monophyletic and that river species have likely contributed significantly to Malawi genomes. Coalescent simulations support the hypothesis that river cichlids have transported polymorphism between lake assemblages. We observed strong genetic differentiation between Malawi lineages for approximately 8% of loci, with contributions from both genic and nongenic SNPs. Notably, more than half of these outlier loci between Malawi groups are polymorphic outside of the lake. Cichlid fishes have evolved diversity in Lake Malawi as new mutations combined with standing genetic variation shared across East Africa.

A test of genetic association among male nuptial coloration, female mating preference, and male aggression bias within a polymorphic population of cichlid fish

Both inter- and intrasexual selection have been implicated in the origin and maintenance of species-rich taxa with diverse sexual traits. Simultaneous disruptive selection by female mate choice and male-male competition can, in theory, lead to speciation without geographical isolation if both act on the same male trait. Female mate choice can generate discontinuities in gene flow, while male-male competition can generate negative frequency-dependent selection stabilizing the male trait polymorphism. Speciation may be facilitated when mating preference and/or aggression bias are physically linked to the trait they operate on. We tested for genetic associations among female mating preference, male aggression bias and male coloration in the Lake Victoria cichlid Pundamilia. We crossed females from a phenotypically variable population with males from both extreme ends of the phenotype distribution in the same population (blue or red). Male offspring of a red sire were significantly redder than males of a blue sire, indicating that intra-population variation in male coloration is heritable. We tested mating preferences of female offspring and aggression biases of male offspring using binary choice tests. There was no evidence for associations at the family level between female mating preferences and coloration of sires, but dam identity had a significant effect on female mate preference. Sons of the red sire directed significantly more aggression to red than blue males, whereas sons of the blue sire did not show any bias. There was a positive correlation among individuals between male aggression bias and body coloration, possibly due to pleiotropy or physical linkage, which could facilitate the maintenance of color polymorphism.

Consistency of thromboelastometry analysis under scrutiny: Results of a systematic evaluation within and between analysers.

While the use of thromboelastometry analysis (ROTEM®) in evaluation of haemostasis is rapidly increasing, important validity parameters of testing remain inadequately examined. We aimed to study systematically the consistency of thromboelastometry parameters within individual tests regarding measurements between different analysers, between different channels of the same analyser, between morning and afternoon measurements (circadian variation), and if measured four weeks apart. Citrated whole blood samples from 40 healthy volunteers were analysed with two analysers in parallel. EXTEM, INTEM, FIBTEM, HEPTEM and APTEM tests were conducted. A Bland-Altman comparison was performed and homogeneity of variances was tested using the pitman test. P-value ranges were used to classify the level of homogeneity (p<0.15 - low homogeneity, p = 0.15 to 0.5 - intermediate homogeneity, p>0.5 high homogeneity). Less than half of all comparisons made showed high homogeneity of variances (p>0.5) and in about a fifth of comparisons data distributions were heterogeneous (p<0.15). There was no clear pattern for homogeneity. On average, comparisons of MCF, ML and LI30 measurements tended to be better, but none of the tests assessed outperformed another. In conclusion, systematic investigation reveals large differences in the results of some thromboelastometry parameters and lack of consistency. Clinicians and scientists should take these inconsistencies into account and focus on parameters with a higher homogeneity such as MCF.

Does Sex Speed Up Evolutionary Rate and Increase Biodiversity?

Most empirical and theoretical studies have shown that sex increases the rate of evolution, although evidence of sex constraining genomic and epigenetic variation and slowing down evolution also exists. Faster rates with sex have been attributed to new gene combinations, removal of deleterious mutations, and adaptation to heterogeneous environments. Slower rates with sex have been attributed to removal of major genetic rearrangements, the cost of finding a mate, vulnerability to predation, and exposure to sexually transmitted diseases. Whether sex speeds or slows evolution, the connection between reproductive mode, the evolutionary rate, and species diversity remains largely unexplored. Here we present a spatially explicit model of ecological and evolutionary dynamics based on DNA sequence change to study the connection between mutation, speciation, and the resulting biodiversity in sexual and asexual populations. We show that faster speciation can decrease the abundance of newly formed species and thus decrease long-term biodiversity. In this way, sex can reduce diversity relative to asexual populations, because it leads to a higher rate of production of new species, but with lower abundances. Our results show that reproductive mode and the mechanisms underlying it can alter the link between mutation, evolutionary rate, speciation and biodiversity and we suggest that a high rate of evolution may not be required to yield high biodiversity.