Cohort profile: the Siyakhula cohort, rural South Africa

No abstract available

Evolution of reduced post-copulatory molecular interactions in Drosophila populations lacking sperm competition.

In many species with internal fertilization, molecules transferred in the male ejaculate trigger and interact with physiological changes in females. It is controversial to what extent these interactions between the sexes act synergistically to mediate the female switch to a reproductive state or instead reflect sexual antagonism evolved as a by product of sexual selection on males. To address this question, we eliminated sexual selection by enforcing monogamy in populations of Drosophila melanogaster for 65 generations and then measured the expression of male seminal fluid protein genes and genes involved in the female response to mating. In the absence of sperm competition, male and female reproductive interests are perfectly aligned and any antagonism should be reduced by natural selection. Consistent with this idea, males from monogamous populations showed reduced expression of seminal fluid protein genes, 16% less on average than in polygamous males. Further, we identified 428 genes that responded to mating in females. After mating, females with an evolutionary history of monogamy exhibited lower relative expression of genes that were up regulated in response to mating and higher expression of genes that were down-regulated - in other words, their post-mating transcriptome appeared more virgin-like. Surprisingly, these genes showed a similar pattern even before mating, suggesting that monogamous females evolved to be less poised for mating and the accompanying receipt of male seminal fluid proteins. This reduced investment by both monogamous males and females in molecules involved in post-copulatory interactions points to a pervasive role of sexual conflict in shaping these interactions

Permeation of CO2 and N2 through glassy poly(dimethyl phenylene) oxide under steady- and presteady-state conditions

Glassy polymers are often used for gas separations because of their high selectivity. Although the dual-mode permeation model correctly fits their sorption and permeation isotherms, its physical interpretation is disputed, and it does not describe permeation far from steady state, a condition expected when separations involve intermittent renewable energy sources. To develop a more comprehensive permeation model, we combine experiment, molecular dynamics, and multiscale reaction–diffusion modeling to characterize the time-dependent permeation of N2 and CO2 through a glassy poly(dimethyl phenylene oxide) membrane, a model system. Simulations of experimental time-dependent permeation data for both gases in the presteady-state and steady-state regimes show that both single- and dual-mode reaction–diffusion models reproduce the experimental observations, and that sorbed gas concentrations lag the external pressure rise. The results point to environment-sensitive diffusion coefficients as a vital characteristic of transport in glassy polymers

Thoughts of self-harm in early and late pregnancy in urban South Africa: Investigating prevalence, predictors and screening options

Background. Thoughts of self-harm (TSH) are an important marker of mental health risk, and risk for attempted and completed suicide. While there is increasing attention being paid to mental health problems in pregnancy in South Africa (SA), TSH have received less attention despite some cross-sectional studies suggesting that prevalence may be high (12 - 39%). There is a dearth of longitudinal research to inform prevention and treatment.Objectives. To examine the rates of TSH across pregnancy in a longitudinal SA cohort and to investigate factors associated with the onset and persistence of TSH, as well as the relationship between TSH, depression and/or anxiety.Methods. Women were enrolled in a prospective pregnancy cohort (S1000) in Soweto, SA between 2014 and 2016, and assessed using validated screening measures (Edinburgh Postnatal Depression Scale (EPDS) and State Trait Anxiety Index short form) in early and later pregnancy. Data were available for 649 women. TSH were determined using EPDS item 10. Logistic regression and bifactor models were used to determine factors associated with TSH across pregnancy.Results. Of the 649 women, 18% reported TSH at some stage during their pregnancy. Prevalence of TSH was slightly higher in early pregnancy (12.5%) than later in pregnancy (11.6%). TSH were associated with a history of mental illness (adjusted odds ratio (aOR) 4.17; 95% confidence interval (CI) 1.3 - 13.7; p=0.020), concurrent depression (aOR 4.8; 95%CI 2.7 - 8.6; p<0.001); marital stress (aOR 1.74; 95% CI 1.0 - 3.0; p=0.040); and practical support (aOR 0.43; 95% CI 0.2 - 1.0; p=0.040) using a multivariate logistic regression. Bifactor analysis examining depression and anxiety scales showed that TSH contributed the highest variance to a shared depression and anxiety factor in early pregnancy. Logistic regressions showed that early depression was a strong predictor of later reports of TSH.Conclusions. The present study shows that the risk of TSH during pregnancy is relatively common, and starts early during pregnancy. Screening approaches could be simplified to encourage healthcare practitioners working in busy and over-burdened public healthcare settings to engage in identifying at-risk women. Efforts in improving early identification of mental health risk in pregnancy should be matched with strengthening of current treatment and referral options. Since practical support and a good marital relationship reduce the risk of TSH, these may be important avenues of focus for designing interventions

Acoustic Emission from Paper Fracture

We report tensile failure experiments on paper sheets. The acoustic emission energy and the waiting times between acoustic events follow power-law distributions. This remains true while the strain rate is varied by more than two orders of magnitude. The energy statistics has the exponent $\beta \sim 1.25 \pm 0.10$ and the waiting times the exponent $\tau \sim 1.0 \pm 0.1$, in particular for the energy roughly independent of the strain rate. These results do not compare well with fracture models, for (brittle) disordered media, which as such exhibit criticality. One reason may be residual stresses, neglected in most theories.Comment: 4 pages, 5 figure

Inferring Deleterious-Mutation Parameters in Natural Daphnia Populations

Deng and Lynch (1, 2) proposed to characterize deleterious genomic mutations from changes in the mean and genetic variance of fitness traits upon selfing in outcrossing populations. Such observations can be readily acquired in cyclical parthenogens. Selfing and life-table experiments were performed for two such Daphnia populations. A significant inbreeding depression and an increase of genetic variance for all traits analyzed were observed. Deng and Lynch's (2) procedures were employed to estimate the genomic mutation rate (U), mean dominance coefficient ( [Image: see text] ), mean selection coefficient ( [Image: see text] ), and scaled genomic mutational variance ( [Image: see text] ). On average, [Image: see text] , [Image: see text] , [Image: see text] and [Image: see text] (^ indicates an estimate) are 0.84, 0.30, 0.14 and 4.6E-4 respectively. For the true values, the [Image: see text] and [Image: see text] are lower bounds, and [Image: see text] and [Image: see text] upper bounds

Maternal alcohol use and children’s emotional and cognitive outcomes in rural South Africa

Background. Alcohol use in South Africa (SA) is increasing. The World Health Organization (WHO) states that SA is the third-largest drinking population in Africa, with the highest rate of fetal alcohol syndrome in the world. Internationally, parental drinking during childhood is a risk factor for poor child mental health, behavioural problems and weaker educational outcomes in middle childhood. However, parental alcohol use in Africa is under-researched, and much of the literature on maternal alcohol consumption is restricted to clinical and pregnancy samples.Objectives. To investigate alcohol use and hazardous drinking (HD) among mothers/primary caregivers of children aged 7 - 11 years in a rural SA cohort. We explored risk factors for drinking and the association between HD and child behaviour/cognition.Methods. The primary outcome measure was the WHO Alcohol Use Disorder Identification Test (AUDIT) using the standardised cut-off for HD (≥8). Secondary measures were the Patient Health Questionnaire Depression Scale (PHQ-9), Patient Health Questionnaire General Anxiety Disorder Scale (GAD-7), Parenting Stress Index, short form (PSI-36), Child Behaviour Checklist (CBCL, parent reported), Kaufman Developmental Assessment Battery (KABC-II) for child cognition, and Neuropsychological Assessment Battery, 2nd edition, subtests (NEPSY-II) for executive function. We compared characteristics of those drinking/not drinking, using χ2 tests, and modelled outcomes on parenting stress, cognitive outcomes and CBCL scores for children using logistic regression analysis. We grouped mothers/caregivers engaged in HD to examine its effect on parent/child outcomes using t-tests to test for significant differences.Results. Of 1 505 women (1 266 mothers and 239 caregivers) with 1 536 children, 12% reported consuming alcohol and 3% reported HD. Higher maternal/caregiver age (31 - 40 years, adjusted odds ratio (aOR) 0.57 (95% confidence interval (CI) 0.4 - 0.9); >41 years, aOR 0.30 (95% CI 0.2 - 0.5)), education (matriculation, aOR 0.49 (95% CI 0.3 - 0.9); post matriculation, aOR 0.30 (95% CI 0.1 - 0.6)), and a stable relationship with the father (aOR 0.6 (95% CI 0.4 - 1.0)) were associated with no alcohol use. Food insecurity increased the odds of alcohol use (aOR 1.52 (95% CI 1.1 - 2.1)), while parental mental health (parenting stress, anxiety) and child mental health problems were associated with approximately double the odds of consuming alcohol in univariate analysis. Children of HD mothers/caregivers had higher mean scores for psychological problems (CBCL total score: no HD (mean 45.0) v. HD (mean 48.9); p=0.029) and lower cognitive scores (KABC Learning Scale: no HD (mean 14.3) v. HD (mean 12.8); p=0.017).Conclusions. While HD rates were low, maternal/caregiver alcohol use negatively impacted on parenting and children’s behavioural/cognitive outcomes. International evidence suggests that integrated approaches engaging parents and families may be more effective for parent-child outcomes than individual psychiatric or medical care for the parent on their own.

A damage model based on failure threshold weakening

A variety of studies have modeled the physics of material deformation and damage as examples of generalized phase transitions, involving either critical phenomena or spinodal nucleation. Here we study a model for frictional sliding with long range interactions and recurrent damage that is parameterized by a process of damage and partial healing during sliding. We introduce a failure threshold weakening parameter into the cellular-automaton slider-block model which allows blocks to fail at a reduced failure threshold for all subsequent failures during an event. We show that a critical point is reached beyond which the probability of a system-wide event scales with this weakening parameter. We provide a mapping to the percolation transition, and show that the values of the scaling exponents approach the values for mean-field percolation (spinodal nucleation) as lattice size $L$ is increased for fixed $R$. We also examine the effect of the weakening parameter on the frequency-magnitude scaling relationship and the ergodic behavior of the model

Deleterious Mutation Burden and Its Association with Complex Traits in Sorghum (Sorghum bicolor)

Sorghum (Sorghum bicolor L.) is a major food cereal for millions of people worldwide. The sorghum genome, like other species, accumulates deleterious mutations, likely impacting its fitness. The lack of recombination, drift, and the coupling with favorable loci impede the removal of deleterious mutations from the genome by selection. To study how deleterious variants impact phenotypes, we identified putative deleterious mutations among ∼5.5 M segregating variants of 229 diverse biomass sorghum lines. We provide the whole-genome estimate of the deleterious burden in sorghum, showing that ∼33% of nonsynonymous substitutions are putatively deleterious. The pattern of mutation burden varies appreciably among racial groups. Across racial groups, the mutation burden correlated negatively with biomass, plant height, specific leaf area (SLA), and tissue starch content (TSC), suggesting that deleterious burden decreases trait fitness. Putatively deleterious variants explain roughly one-half of the genetic variance. However, there is only moderate improvement in total heritable variance explained for biomass (7.6%) and plant height (average of 3.1% across all stages). There is no advantage in total heritable variance for SLA and TSC. The contribution of putatively deleterious variants to phenotypic diversity therefore appears to be dependent on the genetic architecture of traits. Overall, these results suggest that incorporating putatively deleterious variants into genomic models slightly improves prediction accuracy because of extensive linkage. Knowledge of deleterious variants could be leveraged for sorghum breeding through either genome editing and/or conventional breeding that focuses on the selection of progeny with fewer deleterious alleles

Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis

ABSTRACT Mycobacterium kansasii is an environmental nontuberculous mycobacterium that causes opportunistic tuberculosis-like disease. It is one of the most closely related species to the Mycobacterium tuberculosis complex. Using M. kansasii as a proxy for the M. kansasii-M. tuberculosis common ancestor, we asked whether introducing the M. tuberculosis-specific gene pair Rv3377c-Rv3378c into M. kansasii affects the course of experimental infection. Expression of these genes resulted in the production of an adenosine-linked lipid species, known as 1-tuberculosinyladenosine (1-TbAd), but did not alter growth in vitro under standard conditions. Production of 1-TbAd enhanced growth of M. kansasii under acidic conditions through a bacterial cell-intrinsic mechanism independent of controlling pH in the bulk extracellular and intracellular spaces. Production of 1-TbAd led to greater burden of M. kansasii in the lungs of C57BL/6 mice during the first 24 h after infection, and ex vivo infections of alveolar macrophages recapitulated this phenotype within the same time frame. However, in long-term infections, production of 1-TbAd resulted in impaired bacterial survival in both C57BL/6 mice and Ccr2−/− mice. We have demonstrated that M. kansasii is a valid surrogate of M. tuberculosis to study virulence factors acquired by the latter organism, yet shown the challenge inherent to studying the complex evolution of mycobacterial pathogenicity with isolated gene complementation. IMPORTANCE This work sheds light on the role of the lipid 1-tuberculosinyladenosine in the evolution of an environmental ancestor to M. tuberculosis. On a larger scale, it reinforces the importance of horizontal gene transfer in bacterial evolution and examines novel models and methods to provide a better understanding of the subtle effects of individual M. tuberculosis-specific virulence factors in infection settings that are relevant to the pathogen