Strong reciprocity or strong ferocity? A population genetic view of the evolution of altruistic punishment.

Strong reciprocity, defined as a predisposition to help others and to punish those that are not helping, has been proposed as a potent force leading to the evolution of cooperation and altruism. However, the conditions under which strong reciprocity might be favored are not clear. Here we investigate the selective pressure on strong reciprocity by letting both limited dispersal (i.e., spatial structure) and recombination between helping and punishment jointly determine the evolutionary dynamics of strong reciprocity. Our analytical model suggests that when helping and punishment are perfectly linked traits (no recombination occurring between them), strong reciprocity can spread even when the initial frequency of strong reciprocators is close to 0 in the population (i.e., a rare mutant can invade). By contrast, our results indicate that when recombination can occur between helping and punishment (i.e., both traits coevolve) and is stronger than selection, punishment is likely to invade a population of defectors only when it gives a direct fitness benefit to the actor. Overall, our results delineate the conditions under which strong reciprocity is selected for in a spatially structured population and highlight that the forces behind its evolution involves kinship (be it genetic or cultural).

Trypanosoma cruzi: ancestral genomes and population structure

Although the genome of Trypanosoma cruzi has been completely sequenced, little is known about its population structure and evolution. Since 1999, two major evolutionary lineages presenting distinct epidemiological characteristics have been recognised: T. cruzi I and T. cruzi II. We describe new and important aspects of the population structure of the parasite, and unequivocally characterise a third ancestral lineage that we propose to name T. cruzi III. Through a careful analysis of haplotypes (blocks of genes that are stably transmitted from generation to generation of the parasite), we inferred at least two hybridisation events between the parental lineages T. cruzi II and T. cruzi III. The strain CL Brener, whose genome was sequenced, is one such hybrid. Based on these results, we propose a simple evolutionary model based on three ancestral genomes, T. cruzi I, T. cruzi II and T. cruzi III. At least two hybridisation events produced evolutionarily viable progeny, and T. cruzi III was the cytoplasmic donor for the resulting offspring (as identified by the mitochondrial clade of the hybrid strains) in both events. This model should be useful to inform evolutionary and pathogenetic hypotheses regarding T. cruzi.

Determinants and burden of chronic kidney disease in the population-based CoLaus study: a cross-sectional analysis.

BACKGROUND: Chronic kidney disease (CKD) represents an increasing health burden. We present the population-based prevalence of CKD and compare the CKD Epidemiology collaboration (CKD-EPI) and modification of diet in renal disease (MDRD) equations to estimate the glomerular filtration rate, using the revised CKD classification with three albuminuria classes. We also explore factors associated with CKD. METHODS: The Swiss population-based, cross-sectional CoLaus study conducted in Lausanne (2003-2006) included 2810 men and 3111 women aged 35-75. CKD prevalence was assessed using CKD-EPI and MDRD equations and albuminuria estimated by the albumin-to-creatinine ratio in spot morning urine. Multivariate logistic regression was used to analyse determinants of CKD. RESULTS: Prevalence [95% confidence interval (CI)] of all stages CKD was 10.0% (9.2-10.8%) with CKD-EPI and 13.8% (12.9-14.6%) with MDRD. Using the revised CKD classification, the prevalence of low-, medium-, high- and very high-risk groups was 90.0, 8.46, 1.18 and 0.35% with CKD-EPI, respectively. With MDRD, the corresponding values were 86.24, 11.86, 1.55 and 0.35%. Using the revised classification, CKD-EPI systematically reclassified people in a lower risk category than MDRD. Age and obesity were more strongly associated with CKD in men [odds ratio (95% CI): 2.23(1.95; 2.56) per 10 years and 3.05(2.08;4.47), respectively] than in women [1.46 (1.29; 1.65) and 1.78 (1.30;2.44), respectively]. Hypertension, type 2 diabetes, serum homocysteine and uric acid were positively independently associated with CKD in men and women. CONCLUSIONS: One in 10 adults suffers from CKD in the population of Lausanne. CKD-EPI systematically reclassifies people in a lower CKD risk category than MDRD. Serum homocysteine and uric acid levels are associated with CKD independently of classical risk factors such as age, hypertension and diabetes.

On the use of principal components in contemporany population genetics: a case study

In human Population Genetics, routine applications of principal component techniques are oftenrequired. Population biologists make widespread use of certain discrete classifications of humansamples into haplotypes, the monophyletic units of phylogenetic trees constructed from severalsingle nucleotide bimorphisms hierarchically ordered. Compositional frequencies of the haplotypesare recorded within the different samples. Principal component techniques are then required as adimension-reducing strategy to bring the dimension of the problem to a manageable level, say two,to allow for graphical analysis.Population biologists at large are not aware of the special features of compositional data and normally make use of the crude covariance of compositional relative frequencies to construct principalcomponents. In this short note we present our experience with using traditional linear principalcomponents or compositional principal components based on logratios, with reference to a specificdataset

Adiponectin and C-reactive protein are positively associated with microalbuminuria in an adult Caucasian population

Objective: Microalbuminuria (MAU) is a marker of early kidney injury and cardiovascular risk. We assessed the association of MAU with plasma adiponectin, leptin and hsCRP, as inflammatory markers, accounting for hypertension, diabetes and obesity. Design and methods: Population based, cross-sectional study in Caucasian subjects aged 35 to 75 years in Lausanne, Switzerland. MAU, measured on spot morning urine, was used either as a continuous (MAU) or dichotomized variable (MA defined as MAU >2.5 and >3.5 mg/mmol creatinine in men and women, respectively). Results: The 2955 women (age 53.3 ± 10.7, mean ± SD years) had mean body mass index (BMI) 24.9 ± 4.5 kg/m. The 2479 men (age 53.1 ± 10.8 years) had mean BMI 27.0 ± 3.9 kg/m². Median hsCRP was 1.3 and 1.3 mg/L, median adiponectin 6.2 and 10.6 mg/mL in men and women, respectively. MA prevalence was 4.9% in women and 9.8% in men. In multivariate regression analysis adjusting for potential confounders (age, sex, hypertension, diabetes, eGFR, BMI, percent fat mass, insulin and smoking), log-transformed MAU was positively associated with hsCRP (P <0.001) and adiponectin (P = 0.002), but not with leptin. The association of adiponectin with MAU was stronger in subjects with low hsCRP, and vice versa (P interaction <0.001). Conclusion: Adiponectin and hsCRP are significant positive determinants of MAU, independently of diabetes, hypertension and fat mass. A negative interaction between hsCRP and adiponectin was found for their effect on MAU. Whether hyperadiponectinemia represents an adequate protective response to vascular stress or has negative causal impact on the development of MAU should be assessed in further studies.

The role of population movement in the epidemiology and control of schistosomiasis in Brazil: a preliminary typology of population movement

This paper examines recent developments in migration studies. It reviews literature related to the potential role of internal population movement in the occurrence of schistosomiasis in Brazil and modifies Prothero's typology of population movement for use in Brazil. This modified classification system may contribute to a better understanding of schistosome transmission as well as improved research and control programs. The results of this study indicate that population movement in Brazil primarily involves economically-motivated rural-urban and interregional movement. However, several movement patterns have become increasingly important in recent years as a result of changing socioeconomic and urbanisation dynamics. These patterns include urban-urban, intracity and urban-rural movement as well as the movement of environmental refugees and tourists. Little is known about the epidemiological significance of these patterns. This paper also highlights the role of social networks in the decision to migrate and to settle. Prothero's classic population movement typology categorises movement as either one-way migrations or circulations and examines them along spatial and temporal scales. However, the typology must be modified as epidemiological information about new patterns becomes available. This paper identifies areas that require further research and offers recommendations that can improve the measurement and spatial analysis of the relationship between population movement and schistosomiasis.

Expression of SCCmec cassette chromosome recombinases in methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.

OBJECTIVES: Methicillin resistance in staphylococci is mediated by the mecA gene, which is carried on the staphylococcal cassette chromosome mec (SCCmec). SCCmec is responsible for vertical and horizontal transfer of methicillin resistance. Horizontal transfer implies first SCCmec excision from the chromosome. Site-specific excision is catalysed by the Ccr recombinases, which are encoded by ccrAB genes located on the cassette. The aim of this study is to determine the promoter activity of ccrAB genes in individual cells of methicillin-resistant Staphylococcus aureus (N315, COL and MW2) and Staphylococcus epidermidis (RP62A). One mutant cured of its SCCmec (N315EX) was also used. Exposure to various stresses was included in the study. METHODS: For each strain, translational promoter-green fluorescent protein (gfp) fusions were used to assess the levels of ccr promoter activity in individual cells. Analyses were performed using epifluorescence microscopy and flow cytometry. RESULTS: ccr promoter activity was observed in only a small percentage of cell populations. This 'bistable' phenotype was strain dependent (GFP was expressed in N315 and RP62A, but not in COL and MW2) and growth dependent (GFP-expressing cells decreased from approximately 3% to 1% between logarithmic and stationary growth phases). The ccr promoter of strain N315 displayed normal promoter activity when expressed in SCCmec-negative N315EX. Likewise, the ccr promoter of strain COL (which was inactive in COL) showed normal N315-like activity when transformed into N315 and N315EX. CONCLUSIONS: SCCmec excision operates through bistability, favouring a small fraction of cells to 'sacrifice' their genomic islands for transfer, while the rest of the population remains intact. Determinants responsible for the activity of the ccr promoter were not located on SCCmec, but were elsewhere on the genome. Thus, the staphylococcal chromosome plays a key role in determining SCCmec stability and transferability.

Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study.

BACKGROUND: Sleep-disordered breathing is associated with major morbidity and mortality. However, its prevalence has mainly been selectively studied in populations at risk for sleep-disordered breathing or cardiovascular diseases. Taking into account improvements in recording techniques and new criteria used to define respiratory events, we aimed to assess the prevalence of sleep-disordered breathing and associated clinical features in a large population-based sample. METHODS: Between Sept 1, 2009, and June 30, 2013, we did a population-based study (HypnoLaus) in Lausanne, Switzerland. We invited a cohort of 3043 consecutive participants of the CoLaus/PsyCoLaus study to take part. Polysomnography data from 2121 people were included in the final analysis. 1024 (48%) participants were men, with a median age of 57 years (IQR 49-68, range 40-85) and mean body-mass index (BMI) of 25·6 kg/m(2) (SD 4·1). Participants underwent complete polysomnographic recordings at home and had extensive phenotyping for diabetes, hypertension, metabolic syndrome, and depression. The primary outcome was prevalence of sleep-disordered breathing, assessed by the apnoea-hypopnoea index. FINDINGS: The median apnoea-hypopnoea index was 6·9 events per h (IQR 2·7-14·1) in women and 14·9 per h (7·2-27·1) in men. The prevalence of moderate-to-severe sleep-disordered breathing (≥15 events per h) was 23·4% (95% CI 20·9-26·0) in women and 49·7% (46·6-52·8) in men. After multivariable adjustment, the upper quartile for the apnoea-hypopnoea index (>20·6 events per h) was associated independently with the presence of hypertension (odds ratio 1·60, 95% CI 1·14-2·26; p=0·0292 for trend across severity quartiles), diabetes (2·00, 1·05-3·99; p=0·0467), metabolic syndrome (2·80, 1·86-4·29; p<0·0001), and depression (1·92, 1·01-3·64; p=0·0292). INTERPRETATION: The high prevalence of sleep-disordered breathing recorded in our population-based sample might be attributable to the increased sensitivity of current recording techniques and scoring criteria. These results suggest that sleep-disordered breathing is highly prevalent, with important public health outcomes, and that the definition of the disorder should be revised. FUNDING: Faculty of Biology and Medicine of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, Ligue Pulmonaire Vaudoise.

Pragmatic approach for interpreting antiretroviral drug concentrations based on a systematic review of population pharmacokinetic studies

Objectives: The study objective was to derive reference pharmacokinetic curves of antiretroviral drugs (ART) based on available population pharmacokinetic (Pop-PK) studies that can be used to optimize therapeutic drug monitoring guided dosage adjustment.¦Methods: A systematic search of Pop-PK studies of 8 ART in adults was performed in PubMed. To simulate reference PK curves, a summary of the PK parameters was obtained for each drug based on meta-analysis approach. Most models used one-compartment model, thus chosen as reference model. Models using bi-exponential disposition were simplified to one-compartment, since the first distribution phase was rapid and not determinant for the description of the terminal elimination phase, mostly relevant for this project. Different absorption were standardized for first-order absorption processes.¦Apparent clearance (CL), apparent volume of distribution of the terminal phase (Vz) and absorption rate constant (ka) and inter-individual variability were pooled into summary mean value, weighted by number of plasma levels; intra-individual variability was weighted by number of individuals in each study.¦Simulations based on summary PK parameters served to construct concentration PK percentiles (NONMEM®).¦Concordance between individual and summary parameters was assessed graphically using Forest-plots. To test robustness, difference in simulated curves based on published and summary parameters was calculated using efavirenz as probe drug.¦Results: CL was readily accessible from all studies. For studies with one-compartment, Vz was central volume of distribution; for two-compartment, Vz was CL/λz. ka was directly used or derived based on the mean absorption time (MAT) for more complicated absorption models, assuming MAT=1/ka.¦The value of CL for each drug was in excellent agreement throughout all Pop-PK models, suggesting that minimal concentration derived from summary models was adequately characterized. The comparison of the concentration vs. time profile for efavirenz between published and summary PK parameters revealed not more than 20% difference. Although our approach appears adequate for estimation of elimination phase, the simplification of absorption phase might lead to small bias shortly after drug intake.¦Conclusions: Simulated reference percentile curves based on such an approach represent a useful tool for interpretating drug concentrations. This Pop-PK meta-analysis approach should be further validated and could be extended to elaborate more sophisticated computerized tool for the Bayesian TDM of ART.

Molecular characterization of regulatory polymorphisms in the promoter region of the STAT6 gene in a Gabonese population

Parasites remain competent invaders of host immunity. Their invasion strategies have proven to impact immunorelevant genes leading to diversity among gene families. We focussed on signal transducer and activator of transcription (STAT6) factor that plays a fundamental role in signal transduction and activation of transcription. Recent studies have highlighted the role of STAT6 variants in control of infection levels. We identified and investigated regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of the STAT6 gene in a group of Gabonese individuals exposed to a variety of parasitic infections. Three promoter variants were identified in 40 individual subjects. We further validated these promoter variants for their allelic gene expression using transient transfection assays. One promoter variant, rs3024944 (G/C), revealed an altered expression of the marker gene. The identification of function-altering SNPs in the promoter may facilitate studying parasite susceptibility in association studies.

Serum phospholipid fatty acid profile and dietary intake in an adult Mediterranean population with cystic fibrosis.

The relative importance of the usual diet in serum phospholipids in subjects with cystic fibrosis (CF) has been poorly studied. To compare the fatty acid profile in serum phospholipids from adult CF subjects with that of healthy subjects, and determine the role of the normal diet in this profile, we studied thirty-seven adult CF subjects with stable pulmonary disease and thirty-seven healthy controls matched for age, sex and nutritional status. A dietary questionnaire was obtained, anthropometric data were recorded, and the fatty acid profile measured by GLC. Compared with the controls, the percentages of myristic, palmitoleic and stearic acids and total MUFA were significantly higher in the CF group, and DHA, linoleic acid, total PUFA and n-6 fatty acids were significantly lower in the CF group. The CF subjects with worse pulmonary function and with pancreatic insufficiency had significantly lower levels of linoleic and n-6 fatty acids. The total energy intake was significantly higher in the CF subjects, although the energy distribution in the CF subjects and the controls was not different for the carbohydrates, lipids and proteins. No differences were detected in fat intake for MUFA (51 (SD 4) v. 52 (SD 4) %) or saturated fatty acids (33.5 (SD 5) v. 31.2 (SD 3.8) %), but the PUFA were slightly lower in the CF subjects (15.4 (SD 4.5) v. 17.4 (SD 4.2) %; P=0.02). The usual dietary intake of fatty acids by adult CF subjects does not appear to explain the difference in the fatty acid profile compared with controls. This suggests an abnormal fatty acid metabolism in CF subjects.

Intake and home use of olive oil or mixed oils in relation to healthy lifestyles in a Mediterranean population. Findings from the prospective Pizarra study.

Discordances exist in epidemiological studies regarding the association between the intake of nutrients and death and disease. We evaluated the social and health profile of persons who consumed olive oil in a prospective population cohort investigation (Pizarra study) with a 6-year follow-up. A food frequency questionnaire and a 7 d quantitative questionnaire were administered to 538 persons. The type of oil used in food preparation was determined by direct measurement of the fatty acids in samples obtained from the kitchens of the participants at baseline and after follow-up for 6 years. The fatty acid composition of the serum phospholipids was used as an endogenous marker of the type of oil consumed. Total fat intake accounted for a mean 40 % of the energy (at baseline and after follow-up). The concordance in intake of MUFA over the study period was high. The fatty acid composition of the serum phospholipids was significantly associated with the type of oil consumed and with fish intake. The concentration of polar compounds and polymers, indicative of degradation, was greater in oils from the kitchens where sunflower oil or refined olive oil was used, in oils used for deep frying and in oils that had been reused for frying five times or more. Consumption of olive oil was directly associated with educational level. Part of the discordance found in epidemiological studies between diet and health may be due to the handling of oils during food preparation. The intake of olive oil is associated with other healthy habits.

Validation of a new tool to assess health-related quality of life in psoriasis: the PSO-LIFE questionnaire.

BACKGROUND Several questionnaires have been used to measure health related quality of life (HRQoL) in patients with psoriasis, few have been adapted for use in Spain; none of them was developed specifically for the Spanish population. The purpose of the study was to validate and assess the sensitivity to change of a new questionnaire to measure HRQOL in patients with psoriasis (PSO-LIFE). METHODS Observational, prospective, multicenter study performed in centers around Spain. Patients with active or inactive psoriasis completed the PSO-LIFE together with other Dermatology Quality of Life Index (DLQI) and Psoriasis Disability Index (PDI). A control group of patients with urticaria or atopic dermatitis was also included. Internal consistency and test-retest reliability of the PSO-LIFE were assessed by calculating Cronbach's alpha and Intraclass Correlation Coefficient (ICC). Validity was assessed by examining factorial structure, the capacity to discriminate between groups, and correlations with other measures. Sensitivity to change was measured using effect sizes. RESULTS The final sample included for analysis consisted of 304 patients and 56 controls. Mean (SD) age of psoriasis patients was 45.3 (14.5) years compared to 38.8 (14) years for controls (p < 0.01). Cronbach's alpha for the PSO-LIFE was 0.95 and test-retest reliability using the ICC was 0.98. Factor analysis showed the questionnaire to be unidimensional. Mean (SD) PSO-LIFE scores differed between patients with psoriasis and controls (64.9 [22.5] vs 69.4 [17.3]; p < 0.05), between those with active and inactive disease (57.4 [20.4] vs 76.4 [20.6]; p < 0.01), and between those with visible and non-visible lesions (63.0 [21.9] vs. 74.8 [23.9]; p < 0.01). The correlation between PSO-LIFE and PASI scores was moderate (r = -0.43) while correlations with DLQI and PDI dimensions ranged from moderate to high (between 0.4 and 0.8). Effect size on the PSO-LIFE in patients reporting 'much improved' health status at study completion was 1.01 (large effect size). CONCLUSIONS The present results provide substantial support for the reliability, validity, and responsiveness of the PSO-LIFE questionnaire in the population for which it was designed.

The effect of combined polymorphisms in chemokines and chemokine receptors on the clinical course of HIV-1 infection in a Brazilian population

Polymorphisms in genes that encode chemokines or their receptors can modulate susceptibility to human immunodeficiency virus (HIV) infection and disease progression. The objective of this study was to assess the frequency of polymorphisms CCR5-Δ32, CCR2-64I, CCR5-59029A and SDF1-3'A and their role in the course of HIV infection in a Southern Brazilian population. Clinical data were obtained from 249 patients for an average period of 6.4 years and genotypes were determined by standard polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism. Survival analyses were conducted for three outcomes: CD4+ T-cell counts below 200 cells/µL, acquired immune deficiency syndrome (AIDS) or death. The frequency of the polymorphisms CCR5-Δ32, CCR2-64I, CCR5-59029A and SDF1-3'A were 0.024, 0.113, 0.487 and 0.207, respectively. CCR5-Δ32 was associated with a reduction in the risk for CD4+ T-cell depletion and with an increased risk for death after AIDS diagnosis. CCR2-64I was associated with a reduction in the risk for developing AIDS. SDF1-3'A was also associated with decreased risk for AIDS, but its effect was only evident when CCR2-64I was present as well. These results highlight the possibility of using these markers as indicators for the prognosis of disease progression and provide evidence for the importance of analysing the effects of gene polymorphisms in a combined fashion.