Diagnostic performance of several biomarkers for identification of cases of non-communicable diseases among Central Africans

Background: This study determined the diagnostic performance of new biomarkers for a composite diagnosis of non-communicable diseases (NCDs) among Central Africans. Methods:  This case-control study was conducted at LOMO Medical Centre, Kinshasa, DR Congo (DRC) between January – December, 2008. The cases comprised 226 participants with concurrent presence of at least 2 or more of NCDs. Anthropometric parameters and blood pressure were measured while blood samples were assayed for biomarkers. The receiver operating characteristics curve and the logistic regression model were applied.Results: Serum selenium (Se) had specificity and sensitivity of 72.4% and 91.1%, respectively with an area under the curve (AUC) of 0.802; Nitric oxide (NO) (specificity: 72.4%; sensitivity: 93.0%) (AUC = 0.800); Thyroid stimulating hormone (TSH) levels > 6 Mu/L (specificity: 75%; sensitivity: 65%) (AUC = 0.0.727); serum calcium levels of ≥ 110g/L (specificity: 76%; sensitivity: 75%) (AUC = 0.822); and daily salt intake of ≥10 g/day (specificity: 75%; sensitivity: 67%) (AUC = 0.653) in the diagnosis of all NCDs, which were all highly significant (<0.0001).  Conclusion: Serum Se, NO, calcium, TSH and daily salt intake had high diagnostic performance as biomarkers for identification of patients with concurrent NCDs in the study population. Keywords: Non-communicable diseases, diet, new biomarkers, Central Africa

Diagnostic performance of several biomarkers for identification of cases of non-communicable diseases among Central Africans

Background: This study determined the diagnostic performance of new biomarkers for a composite diagnosis of non-communicable diseases (NCDs) among Central Africans. Methods: This case-control study was conducted at LOMO Medical Centre, Kinshasa, DR Congo (DRC) between January \u2013 December, 2008. The cases comprised 226 participants with concurrent presence of at least 2 or more of NCDs. Anthropometric parameters and blood pressure were measured while blood samples were assayed for biomarkers. The receiver operating characteristics curve and the logistic regression model were applied. Results: Serum selenium (Se) had specificity and sensitivity of 72.4% and 91.1%, respectively with an area under the curve (AUC) of 0.802; Nitric oxide (NO) (specificity: 72.4%; sensitivity: 93.0%) (AUC = 0.800); Thyroid stimulating hormone (TSH) levels > 6 Mu/L (specificity: 75%; sensitivity: 65%) (AUC = 0.0.727); serum calcium levels of 65 110g/L (specificity: 76%; sensitivity: 75%) (AUC = 0.822); and daily salt intake of 6510 g/day (specificity: 75%; sensitivity: 67%) (AUC = 0.653) in the diagnosis of all NCDs, which were all highly significant (<0.0001). Conclusion: Serum Se, NO, calcium, TSH and daily salt intake had high diagnostic performance as biomarkers for identification of patients with concurrent NCDs in the study population

Gene(s) and individual feeding behavior: Exploring eco-evolutionary dynamics underlying left-right asymmetry in the scale-eating cichlid fish Perissodus microlepis

The scale‐eating cichlid fish Perissodus microlepis is a textbook example of bilateral asymmetry due to its left or right‐bending heads and of negative frequency‐dependent selection, which is proposed to maintain this stable polymorphism. The mechanisms that underlie this asymmetry remain elusive. Several studies had initially postulated a simple genetic basis for this trait, but this explanation has been questioned, particularly by reports observing a unimodal distribution of mouth shapes. We hypothesize that this unimodal distribution might be due to a combination of genetic and phenotypically plastic components. Here, we expanded on previous work by investigating a formerly identified candidate SNP associated to mouth laterality, documenting inter‐individual variation in feeding preference using stable isotope analyses, and testing their association with mouth asymmetry. Our results suggest that this polymorphism is influenced by both a polygenic basis and inter‐individual non‐genetic variation, possibly due to feeding experience, individual specialization, and intraspecific competition. We introduce a hypothesis potentially explaining the simultaneous maintenance of left, right, asymmetric and symmetric mouth phenotypes due to the interaction between diverse eco‐evolutionary dynamics including niche construction and balancing selection. Future studies will have to further tease apart the relative contribution of genetic and environmental factors and their interactions in an integrated fashion

Evolution of Fish in Extreme Environments : Insights from the Magadi tilapia (Alcolapia grahami)

Extreme environments such as soda lakes are largely unexplored habitats where a surprising number of often endemic species thrive regardless of multiple co-occurring abiotic stresses, depleted food resources and restricted dispersal abilities. Their distinct geochemistry, ecological boundaries, simplified biota and high levels of endemism strikingly resemble the features found on islands that have long been used for evolutionary studies. Extreme environments thus represent prime natural laboratories to test various hypotheses related to the evolutionary processes shaping the origin and distribution of biodiversity. In this thesis, I used a multidisciplinary approach to examine how extreme aquatic habitats shape the evolutionary trajectories of their fish populations, using the Magadi tilapia (Alcolapia grahami) as a model species. This small-bodied cichlid fish has evolved to tolerate extreme water conditions (salinity: ~60% seawater, pH above 10, titration alkalinity > 300 mM, osmolality = 525 mOsm, and temperatures often exceeding 40 °C) in the Lake Magadi basin, Kenya.In the first part of my research project (Chapter three), I used neutral markers to characterize five populations of Magadi tilapia representing the entire species range, and to infer the phylogenetic position of the species. With the exception of a single population that is isolated by a land barrier, all the other populations are isolated by trona (expansive layers of floating solidified sodium carbonate salts). The results suggest high genetic diversity and strong genetic structuring of Magadi tilapia populations into three distinct clusters: Little Magadi, Fish Spring Lagoon, and Rest of Magadi. The physically isolated Little Magadi population was the most genetically distinct, whereas three populations separated by trona were genetically indistinguishable (these constitute the Rest of Magadi cluster). Interestingly, one population (Fish Spring Lagoon), which is also isolated from the populations within Lake Magadi by trona, displayed clear genetic differentiation suggesting that trona may play a key role in shaping the genetic structure of Magadi tilapia populations. Phylogenetically, Magadi tilapia grouped closely to a freshwater tilapiine cichlid, Oreochromis variabilis, from Lake Victoria. This is consistent with previous suggestions that the Alcolapia, the genus of which Magadi is a member of, is descended from a freshwater ancestor.In the second part of my research project, building on the results of the first study, I examined the potential occurrence of eco-morphological differentiation among Magadi tilapia populations, taking their past demographic history into account (Chapter four). To achieve this, I integrated data from population genomics, geometric morphometrics, stable isotopes, and demographic analyses. The results again suggested that the physically isolated Little Magadi population is the most genetically distinct. It has a narrow niche breadth and a characteristically upturned mouth, which is likely an adaptation to feeding on prey suspended on the water surface. Subtle ecomorphological differences exist between the populations within Lake Magadi. Notably, the results suggest that the three genetically distinct populations of Magadi tilapia diverged simultaneously rather recently about 1 100 generations ago.In the third component of my research project (Chapter five), I examined gene expression responses of Magadi tilapia to contrasting water conditions (its natural hypersaline water vs. freshwater) and against its closely related freshwater species, Oreochromis leucostictus. A high level of gene expression variation was observed especially between Magadi tilapia and its freshwater relative. Significant expression differences were also observed between wild and freshwater-acclimated samples of Magadi tilapia in genes related to metabolism, osmoregulation and chemical detoxification. This suggests that changes in gene expression may play a role in the adaptation of Magadi tilapia to the extreme environment. Additionally, a set of genes with physiological functions related to responses to water stress and which were surprisingly not differentially expressed were found to be under positive selection in Magadi tilapia. This suggests that evolution of stress tolerance in Magadi tilapia may be driven by both alteration in gene expression and coding sequences. Importantly, I found for the first time, the expression of the complete set of genes in the pathway responsible for urea synthesis in the gills of a teleost fish. This may represent a major physiological adaptation in Magadi tilapia to increase the rate of urea excretion to avoid accumulation of ammonia, which is lethal given its highly alkaline habitat. The differentially expressed genes and the genes showing positive signatures of selection are promising candidate genes for future studies on the genetic adaptations of Magadi tilapia.Taken together, the results of my PhD research revealed strong patterns of population structuring and rapid ecomorphological diversification in an evolutionarily young cichlid lineage as well as important insights into the genomic responses involved in fish adaptation to multiple stressful conditions. Conservation of the Magadi tilapia populations should focus on maintaining the integrity of the unique gene pools identified in this phenotypically distinct group of cichlid fishes

Pronounced genetic differentiation of small, isolated and fragmented tilapia populations inhabiting the Magadi Soda Lake in Kenya

Lake Magadi, an alkaline hypersaline lake in Kenya, is one of the most extreme water bodies known. Although its water temperatures often exceed 40°C, a particular lineage of ‘dwarf’ tilapia, Alcolapia grahami, has evolved remarkable adaptations to survive in this hostile environment. Magadi tilapia exists in small fragmented populations in isolated lagoons within Lake Magadi and its satellite Lake, Little Magadi. In spite of the potential this tilapia holds for understanding evolutionary processes in stressful environments, few genetic studies have focused on this species. We examined the genetic diversity and spatial genetic relationships of Magadi tilapia populations using microsatellite and mitochondrial markers. High levels of genetic variation were found to be supporting the hypothesis that A. grahami populations represent remnants of a much larger fish population that inhabited paleo-lake Orolonga. In contrast to previous studies, we found a well-supported genetic structure of A. grahami consisting of three differentiated genetic clusters (a) Little Magadi, (b) Fish Spring Lagoon and (c) Rest of Magadi. Given the importance of this species to the Magadi ecosystem and its potential evolutionary significance, the three genetic clusters should be considered as separate gene pools and conservation strategies aimed at protecting the species based on these clusters are recommended

Data from: Eco-morphological differentiation in Lake Magadi tilapia, an extremophile cichlid fish living in hot, alkaline and hypersaline lakes in East Africa

Ecological diversification through divergent selection is thought to be a major force during the process of adaptive radiations. However, the large sizes and complexity of most radiations such as those of the cichlids in the African Great Lakes make it impossible to infer the exact evolutionary history of any population divergence event. The genus Alcolapia, a small cichlid lineage endemic to Lakes Magadi and Natron in East Africa, exhibits phenotypes similar to some of those found in cichlids of the radiations of the African Great Lakes. The simplicity within Alcolapia makes it an excellent model system to investigate ecological diversification and speciation. We used an integrated approach including population genomics based on RAD-seq data, geometric morphometrics, and stable isotope analyses to investigate the eco-morphological diversification of tilapia in Lake Magadi and its satellite lake Little Magadi. Additionally, we reconstructed the demographic history of the species using coalescent simulations based on the joint site frequency spectrum. The population in Little Magadi has a characteristically upturned mouth - possibly an adaptation to feeding on prey from the water surface. Eco-morphological differences between populations within Lake Magadi are more subtle, but are consistent with known ecological differences between its lagoons such as high concentrations of nitrogen attributable to extensive guano deposits in Rest of Magadi relative to Fish Springs Lagoon. All populations diverged simultaneously only about 1,100 generations ago. Differences in levels of gene flow between populations and the effective population sizes have likely resulted in the inferred heterogeneous patterns of genome-wide differentiation

Genomics of Adaptation to Multiple Concurrent Stresses : Insights from Comparative Transcriptomics of a Cichlid Fish from One of Earth’s Most Extreme Environments, the Hypersaline Soda Lake Magadi in Kenya, East Africa

The Magadi tilapia (Alcolapia grahami) is a cichlid fish that inhabits one of the Earth's most extreme aquatic environments, with high pH (~10), salinity (~60 % of seawater), high temperatures (~40 °C), and fluctuating oxygen regimes. The Magadi tilapia evolved several unique behavioral, physiological, and anatomical adaptations, some of which are constituent and thus retained in freshwater conditions. We conducted a transcriptomic analysis on A. grahami to study the evolutionary basis of tolerance to multiple stressors. To identify the adaptive regulatory changes associated with stress responses, we massively sequenced gill transcriptomes (RNAseq) from wild and freshwater-acclimated specimens of A. grahami. As a control, corresponding transcriptome data from Oreochromis leucostictus, a closely related freshwater species, were generated. We found expression differences in a large number of genes with known functions related to osmoregulation, energy metabolism, ion transport, and chemical detoxification. Over-representation of metabolism-related gene ontology terms in wild individuals compared to laboratory-acclimated specimens suggested that freshwater conditions greatly decrease the metabolic requirements of this species. Twenty-five genes with diverse physiological functions related to responses to water stress showed signs of divergent natural selection between the Magadi tilapia and its freshwater relative, which shared a most recent common ancestor only about four million years ago. The complete set of genes responsible for urea excretion was identified in the gill transcriptome of A. grahami, making it the only fish species to have a functional ornithine-urea cycle pathway in the gills-a major innovation for increasing nitrogenous waste efficiency.publishe

Eco-morphological differentiation in Lake Magadi tilapia, an extremophile cichlid fish living in hot, alkaline and hypersaline lakes in East Africa

Ecological diversification through divergent selection is thought to be a major force during the process of adaptive radiations. However, the large sizes and complexity of most radiations such as those of the cichlids in the African Great Lakes make it impossible to infer the exact evolutionary history of any population divergence event. The genus Alcolapia, a small cichlid lineage endemic to Lakes Magadi and Natron in East Africa, exhibits phenotypes similar to some of those found in cichlids of the radiations of the African Great Lakes. The simplicity within Alcolapia makes it an excellent model system to investigate ecological diversification and speciation. We used an integrated approach including population genomics based on RAD-seq data, geometric morphometrics and stable isotope analyses to investigate the eco-morphological diversification of tilapia in Lake Magadi and its satellite lake Little Magadi. Additionally, we reconstructed the demographic history of the species using coalescent simulations based on the joint site frequency spectrum. The population in Little Magadi has a characteristically upturned mouth-possibly an adaptation to feeding on prey from the water surface. Eco-morphological differences between populations within Lake Magadi are more subtle, but are consistent with known ecological differences between its lagoons such as high concentrations of nitrogen attributable to extensive guano deposits in Rest of Magadi relative to Fish Springs Lagoon. All populations diverged simultaneously only about 1100 generations ago. Differences in levels of gene flow between populations and the effective population sizes have likely resulted in the inferred heterogeneous patterns of genome-wide differentiation.publishe