Between-population Differences Research Articles

Multiple karyotype differences between populations of the Hoplias malabaricus (Teleostei; Characiformes), a species complex in the gray area of the speciation process.

Neotropical fishes exhibit remarkable karyotype diversity, whose evolution is poorly understood. Here, we studied genetic differences in 60 individuals, from 11 localities of one species, the wolf fish Hoplias malabaricus, from populations that include six different "karyomorphs". These differ in Y-X chromosome differentiation, and, in several cases, by fusions with autosomes that have resulted in multiple sex chromosomes. Other differences are also observed in diploid chromosome numbers and morphologies. In an attempt to start understanding how this diversity was generated, we analyzed within- and between-population differences in a genome-wide sequence data set. We detect clear genotype differences between karyomorphs. Even in sympatry, samples with different karyomorphs differ more in sequence than samples from allopatric populations of the same karyomorph, suggesting that they represent populations that are to some degree reproductively isolated. However, sequence divergence between populations with different karyomorphs is remarkably low, suggesting that chromosome rearrangements may have evolved during a brief evolutionary time. We suggest that the karyotypic differences probably evolved in allopatry, in small populations that would have allowed rapid fixation of rearrangements, and that they became sympatric after their differentiation. Further studies are needed to test whether the karyotype differences contribute to reproductive isolation detected between some H. malabaricus karyomorphs.

A Quadruple Revolution: Deciphering Biological Complexity with Artificial Intelligence, Multiomics, Precision Medicine, and Planetary Health.

A quiet quadruple revolution has been in the making in systems science with convergence of (1) artificial intelligence, machine learning, and other digital technologies; (2) multiomics big data integration; (3) growing interest in the "variability science" of precision/personalized medicine that aims to account for patient-to-patient and between-population differences in disease susceptibilities and responses to health interventions such as drugs, nutrition, vaccines, and radiation; and (4) planetary health scholarship that both scales up and integrates biological, clinical, and ecological contexts of health and disease. Against this overarching background, this article presents and highlights some of the salient challenges and prospects of multiomics research, emphasizing the attendant pivotal role of systems medicine and systems biology. In addition, we emphasize the rapidly growing importance of planetary health research for systems medicine, particularly amid climate emergency, ecological degradation, and loss of planetary biodiversity. Looking ahead, we anticipate that the integration and utilization of multiomics big data and artificial intelligence will drive further progress in systems medicine and systems biology, heralding a promising future for both human and planetary health.

Plastic and genomic change of a newly established lizard population following a founder event.

Understanding how phenotypic divergence arises among natural populations remains one of the major goals in evolutionary biology. As part of competitive exclusion experiment conducted in 1971, 10 individuals of Italian wall lizard (Podarcis siculus (Rafinesque-Schmaltz, 1810)) were transplanted from Pod Kopište Island to the nearby island of Pod Mrčaru (Adriatic Sea). Merely 35 years after the introduction, the newly established population on Pod Mrčaru Island had shifted their diet from predominantly insectivorous towards omnivorous and changed significantly in a range of morphological, behavioural, physiological and ecological characteristics. Here, we combine genomic and quantitative genetic approaches to determine the relative roles of genetic adaptation and phenotypic plasticity in driving this rapid phenotypic shift. Our results show genome-wide genetic differentiation between ancestral and transplanted population, with weak genetic erosion on Pod Mrčaru Island. Adaptive processes following the founder event are indicated by highly differentiated genomic loci associating with ecologically relevant phenotypic traits, and/or having a putatively adaptive role across multiple lizard populations. Diverged traits related to head size and shape or bite force showed moderate heritability in a crossing experiment, but between-population differences in these traits did not persist in a common garden environment. Our results confirm the existence of sufficient additive genetic variance for traits to evolve under selection while also demonstrating that phenotypic plasticity and/or genotype by environment interactions are the main drivers of population differentiation at this early evolutionary stage.

Sex differences in lifetime prevalence of low back pain: A multinational study of opposite-sex twin pairs.

Low back pain (LBP) is more likely to occur in people with a family history of this condition, highlighting the importance of accounting for familial factors when studying the individual risk of LBP. We conducted a study of opposite-sex twin pairs investigating sex differences in LBP while accounting for (genetic and shared environmental) familial factors. We applied a matched co-twin control design to study 795 adult opposite-sex pairs from Australia, Spain, and the United States (US). We used mixed-effects logistic regression to assess the within-pair association between female sex and lifetime prevalence of LBP in unadjusted and adjusted models for body-mass-index, and depression, as well as interactions between female sex and age (<median age vs. ≥median age) in this association. The mean age of the sample was 47.4 years (Standard Deviation = 16.5). The adjusted odds ratio (aOR) of the association between sex and LBP in the merged sample was 1.11 (95% Confidence Interval = 0.88-1.40), with 87.4% of the variance in the studied association explained by between-site heterogeneity (Q test; p = 0.001). Females had 2.37 (95% CI: 1.48-3.78) higher odds of LBP compared to their male co-twins in the Spanish sample (adjusted), but a sex association was not found in the Australian nor US samples. We found no evidence of the association between sex and LBP in our merged sample. Between-population differences (i.e. cultural background or health system characteristics) are likely to be major factors leading to variation in the sex association with LBP when familial factors are accounted for. Our study of adult opposite-sex twin pairs found no evidence of an association between female sex and lifetime prevalence of low back pain after controlling for familial factors in the merged sample from Australia, Spain and USA, contrary to findings from previous studies of unrelated individuals. Our findings indicate potentially relevant between-country genetic, cultural and environmental differences which may need to be considered for optimal and individualized strategies for the prevention and management of low back pain across the lifespan.

Single-Cell RNA Sequencing Reveals Microevolution of the Stickleback Immune System.

The risk and severity of pathogen infections in humans, livestock, or wild organisms depend on host immune function, which can vary between closely related host populations or even among individuals. This immune variation can entail between-population differences in immune gene coding sequences, copy number, or expression. In recent years, many studies have focused on population divergence in immunity using whole-tissue transcriptomics. But, whole-tissue transcriptomics cannot distinguish between evolved differences in gene regulation within cells, versus changes in cell composition within the focal tissue. Here, we leverage single-cell transcriptomic approaches to document signatures of microevolution of immune system structure in a natural system, the three-spined stickleback (Gasterosteus aculeatus). We sampled nine adult fish from three populations with variability in resistance to a cestode parasite, Schistocephalus solidus, to create the first comprehensive immune cell atlas for G. aculeatus. Eight broad immune cell types, corresponding to major vertebrate immune cells, were identified. We were also able to document significant variation in both abundance and expression profiles of the individual immune cell types among the three populations of fish. Furthermore, we demonstrate that identified cell type markers can be used to reinterpret traditional transcriptomic data: we reevaluate previously published whole-tissue transcriptome data from a quantitative genetic experimental infection study to gain better resolution relating infection outcomes to inferred cell type variation. Our combined study demonstrates the power of single-cell sequencing to not only document evolutionary phenomena (i.e., microevolution of immune cells) but also increase the power of traditional transcriptomic data sets.

Mitochondrial Gene Pool of Ukrainians in the Context of Variability of Whole Mitogenomes in Slavic Peoples

Data on the variability of nucleotide sequences of whole mitochondrial genomes in Ukrainians were analyzed. A comparative analysis of genetic diversity parameters showed that Ukrainians, like other European populations, are characterized by a high level of mtDNA diversity. However, between-population differences in Europe are very low (FST = 0.36%, p 0.00001). According to the results of the FST-analysis, Ukrainians show the greatest similarity with Slovaks, Russians, Poles, Serbs, and Estonians. On the graph of multidimensional scaling of FST-distances, Ukrainians are located together with Western and Eastern Slavs, occupying a central position among them. The results of the analysis of the dynamics of the effective population size (Ne) showed differences in the long-term dynamics of Ne between populations of the north and south of Eastern Europe. For Ukrainians and the southwestern Russian populations, a period of sharp population growth was recorded in the Neolithic period (approximately 8.2 thousand years ago), while for Estonians and northwestern Russians, population growth was observed much later, in the Bronze Age (approximately 4.3 thousand years ago). An analysis of data on mtDNA variability in Slavic populations showed that the frequency of ethnic specific mtDNA haplotypes varies quite widely in different ethnic groups, from 1.3% in Slovaks to 10.3% in Poles. The proportion of Slavic-specific mtDNA haplotypes also varies: the least number of such haplotypes was found in Czechs and Serbs (less than 10%), and most of all in Ukrainians (23.6%).

Meta-analysis reveals between-population differences affect the link between glucocorticoids and population health.

Glucocorticoids are a popular tool for monitoring health of animal populations because they can increase with environmental stressors and can indicate chronic stress. However, individual responses to stressors create variation in the glucocorticoid-fitness relationship within populations. The inconsistency in this relationship calls into question the widespread use of glucocorticoids in conservation. We investigated the sources of variation in the glucocorticoid-fitness relationship by conducting a meta-analysis across a diverse set of species exposed to conservation-relevant stressors. We first quantified the extent to which studies inferred population health from glucocorticoids without first validating the glucocorticoid-fitness relationship in their own populations. We also tested whether population-level information like life history stage, sex and species longevity influenced the relationship between glucocorticoids and fitness. Finally, we tested for a universally consistent relationship between glucocorticoids and fitness across studies. We found more than half of peer-reviewed studies published between 2008 and 2022 inferred population health solely based on glucocorticoid levels. While life history stage explained some variation in the relationship between glucocorticoids and fitness, we found no consistent relationship between them. Much of the variation in the relationship could be the result of idiosyncratic characteristics of declining populations, such as unstable demographic structure, that coincided with large amounts of variation in glucocorticoid production. We suggest that conservation biologists capitalize on this variation in glucocorticoid production by declining populations by using the variance in glucocorticoid production as an early warning for declines in population health.

The Age Composition and Postmetamorphic Growth Characteristics of the Moor Frog (Rana arvalis) from Habitats with a Short Activity Season

The between-population and sexual differences in demographic and postmetamorphic growth characteristics were studied in Rana arvalis from several habitats of Khanty-Mansiiskii Autonomous Okrug–Yugra (KhMAO) with a relatively short (about 3.5 months) activity season. Skeletochronology was used for age determination. The annual size increments and the rates of these increments were determined on the base of back-calculated body length at each age. In three of four populations, a higher average age in females but not significant sexual differences in the average body length were revealed. In both males and females of all studied KhMAO populations, the rate of the annual size increment between the 1st and 2nd wintering was maximal. The rate of the annual size increment between the 2nd and 3rd wintering was kept relatively high. In comparison with R. arvalis populations of Bryansk, Moscow, and Kirov oblasts with a longer activity season (seven, six, and five months, respectively), frogs from KhMAO populations had a relatively small average body length at each age and low population averages of the body length. At the same time, the character of between-age dynamics in the rate of the size increments of KhMAO populations enabled us to reveal the effects of counter-gradient selection not yet mentioned in the literature. These effects represent the maintenance of a relatively high rate of annual increments up to the 5th wintering in R. arvalis from KhMAO populations with a short activity season.

Electromyographic Activity of Sternocleidomastoid Muscle in Individuals With Neck Pain and Healthy Volunteers: A Reliability and Between-Group Differences Examination

ObjectivesThe purpose of this study was to evaluate the electromyographic activity of the sternocleidomastoid muscle during the performance of the craniocervical flexion test (CCFT) in individuals with neck pain and healthy volunteers, assess the reliability of this method, and examine possible between-population differences. MethodsElectromyographic activity of the sternocleidomastoid muscles of 22 individuals with neck pain and 22 healthy participants was recorded during the 55 stages of the CCFT. Pain (visual analog scale) and disability (Neck Disability Index) levels and pain duration were recorded for the participants with neck pain. Reliability of electromyography was evaluated with the intraclass correlation coefficient, standard error of measurement, and minimum detectable change. ResultsWithin-day reliability indices of electromyographic activity were very good to excellent (intraclass correlation coefficients, 0.86-0.98; standard error of measurement, 1.8%-7.6%; minimum detectable change, 5.0%-21.1%). For the head-lift normalization method, 2-way analysis of variance revealed significant between-group differences (P < .02); however, these were not clinically significant when reliability test-retest error was considered. Differences between contraction levels were significant (P < .001); however, the group by contraction level interaction factor was nonsignificant. Therefore, the between-groups electromyographic increases noted with increasing contraction levels were similar. No correlation was identified between participants’ electromyography data and pain or disability. ConclusionIn participants with moderate pain, disability, and pain duration, no clear alterations in electromyographic activity of the sternocleidomastoid could be detected with the CCFT. Reliability of the test used was very good.

Tolerability and Reactogenicity Profile of mRNA SARS-Cov-2 Vaccines from a Mass Vaccination Campaign in a Tertiary Hospital: Between-Vaccine and Between-Population Prospective Observational Study (VigilVacCOVID Study).

BackgroundThe comparative safety profile of SARS-Cov2 vaccines requires further characterization in real-world settings.ObjectivesThe aim of the VigilVacCOVID study was to assess the short-term safety of BNT162b2 and mRNA-1273 during the vaccination campaign of healthcare professionals (HCPs) and solid-organ transplant recipients (SOTRs) at a hospital clinic.MethodsWe conducted an observational, prospective, single-center, post-authorization study to characterize short-term adverse reactions (ARs) after vaccination. The primary endpoint was to assess between-vaccine differences (HCPs receiving BNT162b2 or mRNA-1273) and between-population differences (HCPs and SOTRs, both receiving mRNA-1273) in the risk of any ARs. Propensity score and covariate-adjusted multivariate models were used. The key secondary endpoint was to provide a descriptive assessment of the frequencies and intensity distribution of ARs.ResultsWe included 5088 HCPs and 1289 patients. mRNA-1273 showed greater reactogenicity than BNT162b2, with an odds ratio (OR) for any AR of 3.04 (95% confidence interval (CI) 2.48–3.73; p value: < 0.001) and a higher frequency and intensity of reported ARs. Compared with HCPs vaccinated with mRNA-1273, SOTRs showed a lower risk of ARs (OR = 0.36; 95% CI 0.25–0.50), with fewer and less severe ARs. Age, sex, and previous SARS-CoV-2 infection were statistically significant covariates for the risk of any AR. A history of drug allergy was significant in the comparison between vaccines (BNT162b2 vs. mRNA-1273), but not in that between SOTRs and HCPs.ConclusionsOur study shows that mRNA-1273 had greater reactogenicity than BNT162b2. Overall, both vaccines had an adequate tolerability profile. mRNA-1273 vaccination caused fewer ARs with milder severity in SOTRs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40259-022-00543-9.

Population differences in the length and early-life dynamics of telomeres among European pied flycatchers.

Telomere length and shortening rate are increasingly being used as biomarkers for long-term costs in ecological and evolutionary studies because of their relationships with survival and fitness. Both early-life conditions and growth, and later-life stressors can create variation in telomere shortening rate. Studies on between-population telomere length and dynamics are scarce, despite the expectation that populations exposed to varying environmental constraints would present divergent telomere length patterns. The pied flycatcher (Ficedula hypoleuca) is a passerine bird breeding across Eurasia (from Spain to western Siberia) and migrating through the Iberian Peninsula to spend the nonbreeding period in sub-Saharan Africa. Thus, different populations show marked differences in migration distance. We studied the large-scale variation of telomere length and early-life dynamics in the pied flycatcher by comparing six European populations across a north-south gradient (Finland, Estonia, England and Spain) predicting a negative effect of migration distance on adult telomere length, and of nestling growth on nestling telomere dynamics. There were clear population differences in telomere length, with English birds from midlatitudes having the longest telomeres. Telomere length did not thus show consistent latitudinal variation and was not linearly linked to differences in migration distance. Early-life telomere shortening rate tended to vary between populations. Fast growth was associated with shorter telomeres in the early life, but faster nestling growth affected telomeres more negatively in northern than southern populations. While the sources of between-population differences in telomere-related biology remain to be more intensively studied, our study illustrates the need to expand telomere studies at the between-population level.

The Relationship between Religiosity and Cognitive Function among Chinese Older Adults in Chicago

Evidence suggests religiosity may be related to cognitive decline in older adults living in the US and China. However, the relationship between religiosity and cognitive function has not been tested in a Chinese community in the US. Immigration and isolation often cause diasporas to differ from communities where they currently reside and their origin. This study aims to determine the relationship between religiosity, cognitive function, and demographic attributes in a sample of older Chinese adults age 60 to 105 living in the Chicago area (N = 3157). Regression analysis showed participation in organized religion significantly predicted higher global cognitive function (β = 0.031, p < 0.001, N = 3051). Of all cognitive function measures including episodic memory (East Boston Memory Immediate and Delayed Recall Test), perceptual speed (Symbol Digit Modalities Test), working memory (Digit Backwards Test), cognitive impairment (Mini Mental State Examination), and a composite measure of (global cognition), the importance of religion only significantly predicted greater working memory capacity (β = 0.045, p = 0.003, N = 3058). Practicing religion at home had a nonsignificant relationship with all measures of cognitive function. All analyses controlled for the following covariates: gender, education, income, number of children, marital status, and health insurance coverage status. Findings suggest that among aspects of religiosity, organized religious involvement may have a positive association with higher cognitive function. Future research should explore between-population differences in the relationships of social factors, religiosity, and cognition function to determine what practices can best benefit older adults in various communities.

Between-population differences in constitutive and infection-induced gene expression in threespine stickleback.

Vertebrate immunity is a complex system consisting of a mix of constitutive and inducible defences. Furthermore, host immunity is subject to selective pressure from a range of parasites and pathogens which can produce variation in these defences across populations. As populations evolve immune responses to parasites, they may adapt via a combination of (1) constitutive differences, (2) shared inducible responses, or (3) divergent inducible responses. Here, we leverage a powerful natural host‐parasite model system (Gasterosteus aculeatus and Schistochephalus solidus) to tease apart the relative contributions of these three types of adaptations to among‐population divergence in response to parasites. Gene expression analyses revealed limited evidence of significant divergence in constitutive expression of immune defence, and strong signatures of conserved inducible responses to the parasite. Furthermore, our results highlight a handful of immune‐related genes which show divergent inducible responses which may contribute disproportionately to functional differences in infection success or failure. In addition to investigating variation in evolutionary adaptation to parasite selection, we also leverage this unique data set to improve understanding of cellular mechanisms underlying a putative resistance phenotype (fibrosis). Combined, our results provide a case study in evolutionary immunology showing that a very small number of genes may contribute to genotype differences in infection response.

Giant and dwarf females: how to explain the fourfold variation in body size and fecundity in Trichonephila senegalensis (Aranea: Nephilidae)

Abstract Variation in life-history traits within a population is caused by genetic, maternal and environmental factors. We explored the high variability in development time, adult body weight and fecundity in females of the sexually size dimorphic spider Trichonephila senegalensis. Their mothers originated from two habitats—strongly seasonal Namibia and mildly seasonal South Africa—and we reared F1 females under standardized laboratory conditions. We found that a considerable part of the variability in recorded life-history traits is caused by family-specific effects, comprising genetic, maternal and early environmental influences. Furthermore, we show population differences in development time, where females originating from Namibia matured within shorter periods than females from South Africa. Also, the relationship between development time and adult weight differs between the two populations, as a significant correlation is only found in females with Namibian origin. Against common wisdom, there was a weak overall correlation between adult weight and clutch mass. We also found that females make different life-history decisions under increasing rather than under decreasing daylength. Although a considerable part of variability in life-history traits is family-specific, we discuss how the between-population differences in life histories and their trade-offs reflect adaptation to diverse habitats.

Mapping the triple burden of smoking, smokeless tobacco and alcohol consumption among adults in 28,521 communities across 640 districts of India: A sex-stratified multilevel cross-sectional study.

National estimates on tobacco and alcohol consumption are insufficient to guide policy at the sub-national level. This study assessed the sex-stratified prevalence of different types of smoking and smokeless tobacco and alcohol consumption among adults aged 15-49 using the National Family Health Survey (2015-16) at sub-national administrative units. Three-level logistic regression models were applied to quantify the variation at district- and community-level in smoking and consumption of smokeless tobacco and alcohol. A higher prevalence of smoking, smokeless tobacco and alcohol consumption was observed among men. The study found that the considerable unexplained variations in two different forms of tobacco and alcohol consumption among men attributed to between-population differences at district-level and community-level. The between-population differences were even larger at the district- and community-level in tobacco and alcohol consumption among women. Continious assessment of tobacco and alcohol consumption at lower administrative units and the development of evidence-based localised cessation interventions must be integrated with health policy to reduce disease burden and preventable deaths.

Maternal effects shape offspring physiological condition but do not senesce in a wild mammal.

In vertebrates, offspring survival often decreases with increasing maternal age. While many studies have reported a decline in fitness-related traits of offspring with increasing maternal age, the study of senescence in maternal effect through age-specific changes in offspring physiological condition is still at its infancy. We assessed the influence of maternal age and body mass on offspring physiological condition in two populations of roe deer (Capreolus capreolus) subjected to markedly different environmental conditions. We measured seven markers to index body condition and characterize the immune profile in 86 fawns which became recently independent of their known-aged mothers. We did not find striking effects of maternal age on offspring physiological condition measured at 8months of age. This absence of evidence for senescence in maternal effects is likely due to the strong viability selection observed in the very first months of life in this species. Offspring physiological condition was, on the other hand, positively influenced by maternal body mass. Between-population differences in environmental conditions experienced by fawns also influenced their average body condition and immune phenotype. Fawns facing food limitation displayed lower values in some markers of body condition (body mass and haemoglobin levels) than those living in good quality habitat. They also allocated preferentially to humoral immunity, contrary to those living in good conditions, which allocated more to cellular response. These results shed a new light on the eco-physiological pathways mediating the relationship between mother's mass and offspring condition.

Smoking, Smokeless Tobacco and Alcohol Consumption Among Adults in India: A Sub-National Cross-Sectional Study

Background: National estimates of tobacco and alcohol use are insufficient to guide policy at sub-national and district level. This study examines sub-national and district-level prevalence and tobacco and alcohol use and its variations in India. Methods: Data on smoking tobacco, smokeless tobacco (SLT) and alcohol use in adults aged 15-49 was analysed from the National Family Health Survey. Sex-stratified prevalence of each types of tobacco and alcohol use at sub-national administrative units was estimated. We fitted multilevel logistic regressions to quantify the variation at the district and community level in tobacco and alcohol use. Findings: Overall, men used any form of tobacco or alcohol (53%, 52.5–53.4) more than women (7.4%, 95% CI 7.3–7.5). 23.4% (95% CI 23.1-23.9) smoked tobacco, with higher use of any SLT (29%, 28.6-29.4) and alcohol (29.2% 28.7-29.6). Women mostly used SLT (5.6%). Cigarette (13.6%, 13.3–14.0) and bidi (13.2%, 12.9–13.5) were most commonly and almost equally used types of smoking tobacco among men. Gutkha/paan masala with tobacco was the most consumed SLT product among both men (15.3%, 15.0–15.6) and women (2.2%, 2.1–2.3), followed by khaini. Beer was the most commonly used alcohol among men, followed by hard liquor. We found that considerable unexplained variation in tobacco and alcohol use attributed to between-population differences at districts (3.5% in smoking, 4% in alcohol and 6% in SLT) and community level (14.9% in smoking, 19.7% in alcohol and 21.5% in SLT) among males. Among females, between-population differences were even larger at districts (16.6% in smoking, 18% in SLT and 29.9% in alcohol) and community level (35.4% in smoking, 32.8% in SLT and 44% in alcohol). Interpretation: Regular assessment of sub-national tobacco and alcohol consumption across different population groups along with development of local cessation interventions must be integrated with health policy to reduce disease burden and preventable deaths. Funding Statement: No specific funding received for this study Declaration of Interests: All the authors declare that they have no conflict of interest. Ethics Approval Statement: The study was reviewed by the National Institute of Cancer Prevention and Research Institutional Ethics Committee and was exempted from full review as the study was based on an anonymous public use dataset with no identifiable information on the study participants.

Explaining Within- vs Between-Population Variation in Child Anthropometry and Hemoglobin Measures in India: A Multilevel Analysis of the National Family Health Survey 2015-2016.

BackgroundThe complex etiology of child growth failure and anemia—commonly used indicators of child undernutrition—involving proximate and distal risk factors at multiple levels is generally recognized. However, their independent and joint effects are often assessed with no clear conceptualization of inferential targets.MethodsWe utilized hierarchical linear modeling and a nationally representative sample of 139,116 children aged 6–59 months from India (2015–2016) to estimate the extent to which a comprehensive set of 27 covariates explained the within- and between-population variation in height-for-age, weight-for-age, weight-for-height, and hemoglobin level.ResultsMost of the variation in child anthropometry and hemoglobin measures was attributable to within-population differences (80–85%), whereas between-population differences (including communities, districts, and states) accounted for only 15–20%. The proximate and distal covariates explained 0.2–7.5% of within-population variation and 2.1–34.0% of between-population variation, depending on the indicator of interest. Substantial heterogeneity was observed in the magnitude of within-population variation, and the fraction explained, in child anthropometry and hemoglobin measures across the 36 states/union territories of India.ConclusionsPolicies and interventions aimed at reducing between-population inequalities in child undernutrition may require a different set of components than those concerned with within-population inequalities. Both are needed to promote the health of the general population, as well as that of high-risk children.

Female immunity in response to sexually transmitted opportunistic bacteria in the common bedbug Cimex lectularius

Besides typical sexually transmitted microbes, even environmental, opportunistic microbes have been found in copulatory organs of insects and even humans. To date, only one study has experimentally investigated the sexual transmission of opportunistic microbes from male to female insects, whereas nothing is known about the transmission from females to males. Even if opportunistic microbes do not cause infection upon transmission, they might eventually become harmful if they multiply inside the female. While the immune system of females is often assumed to target sexually transmitted microbes, most studies ignore the role of mating-associated opportunistic microbes. Variation in immunity between populations has been linked to parasite or bacteria prevalence but no study has ever addressed between-population differences in immune responses to sexually transmitted opportunistic microbes. We here show that bacteria applied to the copulatory organs of common bedbugs, Cimex lectularius, are sexually transmitted to the opposite sex at a high rate, including the transmission from female to male. Bacterial growth in the female sperm-receiving organ was inhibited over the first hours after introduction, but after this initial inhibition bacterial numbers increased, suggesting a shift of investment from immune defence towards reproduction. However, 24 h after the injection of bacteria, male components, or saline as a control, the sperm-receiving organ showed lysozyme-like activity and inhibited the growth of Gram-negative and Gram-positive bacteria in vitro, potentially to mop up the remaining bacteria. Contrasting our prediction, neither bacterial growth nor immune responses differed between populations. Future studies should link transmission dynamics, immune responses and fitness effects in both sexes. Experimental manipulation of environmental bacteria could be used to investigate how transmission frequency and toxicity of sexually transmitted opportunistic microbes shapes bacteria clearance and immune responses across populations.

Impact of Population and Pharmacogenetics Variations on Efavirenz Pharmacokinetics and Immunologic Outcomes During Anti-Tuberculosis Co-Therapy: A Parallel Prospective Cohort Study in Two Sub-Sahara African Populations.

Efavirenz-based combination antiretroviral-therapy (cART) is the recommended regimen during tuberculosis (TB) therapy. In a multi-national parallel prospective-cohort study, we investigated the impact of population and pharmacogenetic variations for efavirenz pharmacokinetics, auto-induction, and immunologic outcome during antituberculosis treatment. A total of 921 treatment-naïve HIV patients with (196 Ethiopians and 231 Tanzanians) or without TB co-infection (285 Ethiopians and 209 Tanzanians) were enrolled and treated with efavirenz-based cART. TB-HIV patients started rifampicin-based anti-TB therapy 4 weeks before cART. Efavirenz plasma concentrations were measured on the 4th and 16th weeks of cART. Genotyping for CYP2B6, CYP3A5, ABCB1, UGT2B7, and SLCO1B1 was done. CD4 cells-count was measured at baseline, 12th, 24th, and 48th weeks of cART. Among HIV-only cohort, plasma efavirenz concentration and median CD4 cell count were significantly higher in Tanzanians than Ethiopians, and both CYP2B6 genotype and population-variation were significant predictors of efavirenz plasma concentration. Within-population analyses indicated a pronounced efavirenz autoinduction in Tanzanians as reflected by a significant decrease of plasma efavirenz concentration over time (p = 0.0001), but not in Ethiopians. Among TB-HIV cohort, there were no significant between-population differences in plasma efavirenz concentrations or CD4 cell-recovery, and CYP2B6 genotype but not population-variation was a significant predictor of efavirenz plasma exposure. In Tanzanian patients, short-term anti-TB co-treatment significantly reduced the mean plasma efavirenz concentration in CYP2B6*1/*1 genotype at week-4 (p = 0.005), but not at week-16 of cART. In Ethiopian patients, anti-TB cotreatment increased the mean plasma efavirenz concentration among CYP2B6*6 carriers at week-4 (p = 0.003) and week-16 (p = 0.035) of cART. In general, long-term anti-TB co-treatment increased plasma efavirenz concentration at week 16 of cART in both Ethiopians and Tanzanians being higher in CYP2B6*6/*6 > *1/*6 > *1/*1 genotypes. In TB-HIV patients, baseline body mass index (BMI), viral load, and WHO clinical-stage but not genotype, population-variation, or efavirenz concentration were significant predictors of immunologic outcome at week-48. In summary efavirenz auto-induction, pharmacokinetics, and the immunologic outcome are influenced by population-variation, anti-TB co-medication, and CYP2B6 genotype. CYP2B6 genotype is a significant predictor of efavirenz plasma exposure regardless of population-variation or antituberculosis co-treatment, but population-variation is insignificant during antituberculosis treatment. CYP2B6 genotype, population, and geographic differences need to be considered for efavirenz dosage-optimization.