Does perceived caregiver HIV stigma and depression increase adolescent neuro-behavioral difficulties? A mediation analysis in the Asenze Cohort.

People living with HIV (PLWH) often experience HIV related stigma that is, in turn, associated with several negative health outcomes including depression, harmful drinking, and intimate partner violence. Despite knowledge of these proximal impacts of HIV stigma on PLWH, less is known about the impact that Caregivers living with HIV's perception of stigma has on the health and behavior of adolescents in their care. Utilizing data from adolescents and their primary caregivers from the population-based Asenze cohort study in KwaZulu-Natal, South Africa, we conducted a path analysis to determine if caregiver depression [operationalized as mental health functioning] is a mediator of the hypothesized association between caregiver HIV stigma and adolescent neurodevelopmental behavior including internalizing and externalizing behaviors.

Measuring the cost-effectiveness of a home-visiting intervention to promote early child development among rural families linked to the Rwandan social protection system.

Early childhood development (ECD) programmes are heralded as a way to improve children's health and educational outcomes. However, few studies in developing countries calculate the effectiveness of quality early childhood interventions. This study estimates the cost and cost-effectiveness of the Sugira Muryango (SM) trial, a home-visiting intervention to improve ECD outcomes through positive parent-child relationships.

The impact of family support and organization on adolescents during school closure under Covid-19 lockdown regulations in an area of South Africa.

The Covid-19 pandemic and resultant disruptions to schooling presented significant challenges for many families. Well organised families have been shown to have a protective effect on adolescent wellbeing in periods of shock. At the onset of the Covid-19 pandemic, Asenze, a population-based cohort study, was conducting a third wave of data collection in peri-urban South Africa, examining risk and protective factors during adolescence.

A mixed-model approach for estimating drivers of microbiota community composition and differential taxonomic abundance.

Next-generation sequencing (NGS) and metabarcoding approaches are increasingly applied to wild animal populations, but there is a disconnect between the widely applied generalized linear mixed model (GLMM) approaches commonly used to study phenotypic variation and the statistical toolkit from community ecology typically applied to metabarcoding data. Here, we describe the suitability of a novel GLMM-based approach for analyzing the taxon-specific sequence read counts derived from standard metabarcoding data. This approach allows decomposition of the contribution of different drivers to variation in community composition (e.

Development of a hydroxyflavone-labelled 4554W peptide probe for monitoring αS aggregation.

Parkinson's is the second most common neurodegenerative disease, with the number of individuals susceptible due to increase as a result of increasing life expectancy and a growing worldwide population. However, despite the number of individuals affected, all current treatments for PD are symptomatic-they alleviate symptoms, but do not slow disease progression. A major reason for the lack of disease-modifying treatments is that there are currently no methods to diagnose individuals during the earliest stages of the disease, nor are there any methods to monitor disease progression at a biochemical level.

Investing in human development and building state resilience in fragile contexts: A case study of early nutrition investments in Burkina Faso.

Maternal and early malnutrition have negative health and developmental impacts over the life-course. Consequently, early nutrition support can provide significant benefits into later life, provided the later life contexts allow. This study examines the limits of siloed investments in nutrition and illustrates how ignoring life-course contextual constraints limits human development benefits and exacerbates inequality, particularly in fragile contexts.

Anionic lipid vesicles have differential effects on the aggregation of early onset-associated α-synuclein missense mutants.

α-synuclein (αS) is the key component of synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies, and multiple system atrophy. αS was first linked to PD through the identification of point mutations in the SNCA gene, causing single amino acid substitutions within αS and familial autosomal dominant forms of PD that profoundly accelerated disease onset by up to several decades. At least eight single-point mutations linked to familial PD (A30G/P, E46K, H50Q, G51D, and A53T/E/V) are located in proximity of the region preceding the non-β amyloid component (preNAC) region, strongly implicating its pathogenic role in αS-mediated cytotoxicity.

Library-Derived Peptide Aggregation Modulators of Parkinson's Disease Early-Onset α-Synuclein Variants.

Parkinson's Disease (PD) is characterized by the accumulation of Lewy bodies in dopaminergic neurons. The main protein component of Lewy bodies, α-synuclein (αS), is also firmly linked to PD through the identification of a number of single point mutations that are autosomal dominant for early-onset disease. Consequently, the misfolding and subsequent aggregation of αS is thought to be a key stage in the development and progression of PD.

The Asenze Cohort Study in KwaZulu-Natal, South Africa: protocol and cohort profile.

The Asenze cohort is set in South Africa, a middle-income country impacted by one of the highest global rates of people living with HIV/AIDS and high levels of socioeconomic inequality. This longitudinal population-based cohort of children and their primary caregivers assesses household and caregiver functioning, child health, social well-being, and neuro-development from childhood through adolescence. Almost 1,600 children born at the peak of the human immunodeficiency virus epidemic (2003-2005) were followed (with their primary caregivers) in 3 waves, between 2008 and 2021, at average ages of 5, 7, and 16.

Associations between MHC class II variation and phenotypic traits in a free-living sheep population.

Pathogen-mediated selection (PMS) is thought to maintain the high level of allelic diversity observed in the major histocompatibility complex (MHC) class II genes. A comprehensive way to demonstrate contemporary selection is to examine associations between MHC variation and individual fitness. As individual fitness is hard to measure, many studies examine associations between MHC variation and phenotypic traits, including direct or indirect measures of adaptive immunity thought to contribute to fitness.

A Downsized and Optimised Intracellular Library-Derived Peptide Prevents Alpha-Synuclein Primary Nucleation and Toxicity Without Impacting Upon Lipid Binding.

Misfolding and aggregation of alpha-synuclein (αS) within dopaminergic neurons is a key factor in the development and progression of a group of age-related neurodegenerative diseases, termed synucleinopathies, that include Parkinson's disease (PD). We previously derived a peptide inhibitor from a 209,952-member intracellular library screen by employing the preNAC region (45-54) as a design template. At least six single-point mutations firmly linked to early-onset Parkinson's disease (E46K, H50Q, G51D, A53T/E/V) are located within this region, strongly implicating a pathogenic role within αS that leads to increased cytotoxicity.

Realising the potential human development returns to investing in early and maternal nutrition: The importance of identifying and addressing constraints over the life course.

The benefits of interventions which improve early nutrition are well recognised. These benefits, however, only accrue to the extent that later life circumstances allow. Consequently, in adverse contexts many of the benefits will never be realised, particularly for the most vulnerable, exacerbating inequality.

The association between female reproductive performance and leukocyte telomere length in wild Soay sheep.

Telomere length (TL), typically measured across a sample of blood cells, has emerged as an exciting potential marker of physiological state and of the costs of investment in growth and reproduction within evolutionary ecology. While there is mounting evidence from studies of wild vertebrates that short TL predicts raised subsequent mortality risk, the relationship between reproductive investment and TL is less clear cut, and previous studies report both negative and positive associations. In this study, we examined the relationship between TL and different aspects of maternal reproductive performance in a free-living population of Soay sheep.

The role of maternally transferred antibodies in maternal performance in red deer.

Maternal effects are ubiquitous. Yet, the pathways through which maternal effects occur in wild mammals remain largely unknown. We hypothesise that maternal immune transfer is a key mechanism by which mothers can affect their offspring fitness, and that individual variation in maternally derived antibodies mainly depends on a mother's characteristics and the environmental conditions she experiences.

Heritable variation in telomere length predicts mortality in Soay sheep.

Telomere length (TL) is considered an important biomarker of whole-organism health and aging. Across humans and other vertebrates, short telomeres are associated with increased subsequent mortality risk, but the processes responsible for this correlation remain uncertain. A key unanswered question is whether TL-mortality associations arise due to positive effects of genes or early-life environment on both an individual's average lifetime TL and their longevity, or due to more immediate effects of environmental stressors on within-individual TL loss and increased mortality risk.

Maternally derived anti-helminth antibodies predict offspring survival in a wild mammal.

The transfer of antibodies from mother to offspring provides crucial protection against infection to offspring during early life in humans and domestic and laboratory animals. However, few studies have tested the consequences of variation in maternal antibody transfer for offspring fitness in the wild. Further, separating the immunoprotective effects of antibodies from their association with nutritional resources provided by mothers is difficult.

The Library Derived 4554W Peptide Inhibits Primary Nucleation of α-Synuclein.

Aggregation of α-Synuclein (αS) is widely regarded as a key factor in neuronal cell death, leading to a wide range of synucleinopathies, including Parkinson's Disease. Development of therapeutics has therefore focused on inhibiting aggregation of αS into toxic forms. One such inhibitor, based on the preNAC region αS (4554W), was identified using an intracellular peptide library screen, and subsequently shown to both inhibit formation of αS aggregates while simultaneously lowering toxicity.

Lactoferrin quantification in cattle faeces by ELISA.

Background: Promoting and maintaining health is critical to ruminant welfare and productivity. Within human medicine, faecal lactoferrin is quantified for routine assessment of various gastrointestinal illnesses avoiding the need for blood sampling. This approach might also be adapted and applied for non-invasive health assessments in animals.

Prevalence and number of children living in institutional care: global, regional, and country estimates.

Background: Children living in institutionalised settings are at risk of negative health and developmental outcomes, as well as physical and emotional abuse, yet information on their numbers is scarce. Therefore, the aim of our study was to estimate global-level, regional-level, and country-level numbers and percentages of children living in institutional care.

Methods: In this estimation study, we did a systematic review of peer-reviewed publications and a comprehensive review of surveys and unpublished literature to construct a dataset on children living in institutional care from 136 countries between 2001 and 2018.

The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries).

Much of our knowledge of the drivers of immune variation, and how these responses vary over time, comes from humans, domesticated livestock or laboratory organisms. While the genetic basis of variation in immune responses have been investigated in these systems, there is a poor understanding of how genetic variation influences immunity in natural, untreated populations living in complex environments. Here, we examine the genetic architecture of variation in immune traits in the Soay sheep of St Kilda, an unmanaged population of sheep infected with strongyle gastrointestinal nematodes.

Natural Selection on Antihelminth Antibodies in a Wild Mammal Population.

An effective immune response is expected to confer fitness benefits through improved resistance to parasites but also incur energetic costs that negatively impact fitness-related traits, such as reproduction. The fitness costs and benefits of an immune response are likely to depend on host age, sex, and levels of parasite exposure. Few studies have examined the full extent to which patterns of natural selection on immune phenotypes vary across demographic groups and environments in the wild.

Molecular confirmation of in field mice () from St Kilda has potential to resolve a host-parasite relationship.

Insular wildlife populations provide opportunities to examine biological questions in systems that are relatively closed and potentially tractable, striking examples being the long-term studies of ecology and evolution in the red deer and feral sheep populations on the Hebridean islands of Rum and St Kilda. In the case of parasitology, Understanding of parasitic infections insular wildlife populations in conjunction with knowledge of their origins has the potential to add a fresh perspective to disease control in humans and domestic animals. In the case of parasitology, understanding infections of insular wildlife populations, in conjunction with knowledge of their origins, has the potential to add a fresh perspective to disease control in humans and domestic animals.

A candidate gene approach to study nematode resistance traits in naturally infected sheep.

Sheep naturally acquire a degree of resistant immunity to parasitic worm infection through repeated exposure. However, the immune response and clinical outcome vary greatly between animals. Genetic polymorphisms in genes integral to differential T helper cell polarization may contribute to variation in host response and disease outcome.