Biology subjects

Hoffman, N.

Publications and source records attributed to Hoffman, N..

6 recordsLinked to original sources

bioRxiv2026

Persistent neuroimmune alterations in children who are HIV-exposed but uninfected at age 6-7 years: Associations with language development in a South African birth cohort

BackgroundChildren who are HIV-exposed but uninfected (HEU) are at increased risk of neurodevelopmental delays, yet neuroimmune pathways linking perinatal HIV exposure to school readiness remain unclear. MethodsIn the Drakenstein Child Health Study, 268 children (94 HEU, 174 HIV-unexposed [HU]) underwent magnetic resonance spectroscopy in midline parietal grey and left parietal white matter regions at 6-7 years. Peripheral blood serum immune markers were measured in pregnancy and in children at 6 weeks, 2, 3, and 5 years. Linear mixed-effects models characterised child immune trajectories and linear regressions tested associations with creatine-referenced neurometabolite ratios and school readiness scores. ResultsMothers living with HIV had higher sCD14 and lower MMP-9, NGAL, and GM-CSF than mothers without HIV (p<0.05). Perinatal HIV exposure was associated with altered trajectories of child sCD14, GM-CSF, IL-1{beta}, IL-5, IL-10, and YKL-40. At 6-7 years, children who were HEU had lower parietal grey matter glutamate ratios and lower left parietal white matter choline ratios. By school entry, immune-neurometabolite associations were predominantly driven by child serum markers; IL-8 emerged as a consistent correlate across developmental stages. Children who were HEU had lower language scores than HU peers. Left parietal white matter choline ratios were positively associated with language and overall school readiness in HU children, but not HEU. ConclusionsPerinatal HIV exposure was associated with alterations in immune development, neurometabolites reflecting both white matter maturation and neuronal health, and school readiness. Our findings highlight potential neuroimmune pathways contributing to neurodevelopmental risks in children who are HEU.

neuroscience↗

bioRxiv2025

Maternal and child immune profiles are associated with neurometabolite measures of early-life neuroinflammation in children who are HIV-exposed and uninfected: a South African birth cohort

Children who are HIV-exposed and uninfected (HEU) are at risk of neurodevelopmental delays, which may be partially due to maternal immune dysregulation during pregnancy. This study investigates associations between maternal and child immune profiles and early neurometabolite profiles in HEU and HIV-unexposed (HU) children from a South African birth cohort. A subgroup of 156 children (66 HEU, 90 HU) from the Drakenstein Child Health Study underwent magnetic resonance spectroscopy at age 2-3 years, and maternal and child serum markers were measured at multiple timepoints via immunoassays. In HEU children, serum concentrations of maternal pro-inflammatory cytokines IL-5 ({beta}=0.79, p=0.005) and IL-8 ({beta}=0.64, p=0.02) were associated with myo-inositol ratios in parietal grey and white matter regions, respectively, while child serum MMP-9 at two years was associated with myo-inositol ratios in the midline parietal grey matter ({beta}=1.30, p=0.03). The association of maternal anti-inflammatory cytokine IL-13 with glutamate ratios in the midline parietal grey matter was negative in HEU ({beta}=-0.41, p=0.038) and positive in HU children ({beta}=0.42, p<0.0001). These findings suggest maternal immune activation may affect neurometabolite profiles in HEU children.

neuroscience↗

bioRxiv2024

Impaired Suppression of Plasma Lipid Extraction and its Partitioning Away from Muscle by Insulin in Humans with Obesity

ContextHumans with obesity and insulin resistance exhibit lipid accumulation in skeletal muscle, but the underlying biological mechanisms responsible for the accumulation of lipid in the muscle of these individuals remain unknown. ObjectiveWe investigated how plasma insulin modulates the extraction of circulating triglycerides (TGs) and non-esterified fatty acids (NEFAs) from ingested and endogenous origin in the muscle of lean, insulin-sensitive humans (Lean-IS) and contrasted these responses to those in humans with obesity and insulin resistance (Obese-IR). MethodsThe studies were performed in a postprandial state associated with steady-state plasma TG concentrations. The arterio-venous blood sampling technique was employed to determine the extraction of circulating lipids across the forearm muscle before and after insulin infusion. We distinguished kinetics of TGs and NEFAs from ingested origin from those from endogenous origin across muscle by incorporating stable isotope-labeled triolein in the ingested fat. ResultsInsulin infusion rapidly suppressed the extraction of plasma TGs from endogenous, but not ingested, origin in the muscle of the Lean-IS, but this response was absent in the muscle of the Obese-IR. Furthermore, in the muscle of the Lean-IS, insulin infusion decreased the extraction of circulating NEFAs from both ingested and endogenous origin; however, this response was absent for NEFAs from ingested origin in the muscle of the Obese-IR subjects. ConclusionsPartitioning of circulating lipids away from the skeletal muscle when plasma insulin increases during the postprandial period is impaired in humans with obesity and insulin resistance.

physiology↗

bioRxiv2022

Identifying indels from WGS short reads of haploid genomes distinguishes variant-calling algorithms

Identification of clinically relevant strains of bacteria increasingly relies on whole genome sequencing. The downstream bioinformatics steps necessary for calling variants from short read sequences are well-established but seldom validated against haploid genomes. We devised an in silico workflow to introduce single nucleotide polymorphisms (SNP) and indels into bacterial reference genomes, and computationally generate sequencing reads based on the mutated genomes. We then applied the method to Mycobacterium tuberculosis H37Rv and used the synthetic reads as truth sets for evaluating several popular variant callers. Insertions proved especially challenging for most variant callers to correctly identify, relative to deletions and single nucleotide polymorphisms. With adequate read depth, however, variant callers that use high quality soft-clipped reads and base mismatches to perform local realignment consistently had the highest precision and recall in identifying medium-length insertions and deletions.

bioinformatics↗

bioRxiv2020

PhosR enables processing and functional analysis of phosphoproteomic data

Mass spectrometry (MS)-based phosphoproteomics has revolutionised our ability to profile phosphorylation-based signalling in cells and tissues on a global scale. To infer the action of kinases and signalling pathways in phosphoproteomic experiments, we present PhosR, a set of tools and methodologies implemented in a suite of R packages facilitating comprehensive analysis of phosphoproteomic data. By applying PhosR to both published and new phosphoproteomic datasets, we demonstrate capabilities in data imputation and normalisation using a novel set of stably phosphorylated sites, and in functional analysis for inferring active kinases and signalling pathways. In particular, we introduce a signalome construction method for identifying a collection of signalling modules to summarise and visualise the interaction of kinases and their collective actions on signal transduction. Together, our data and findings demonstrate the utility of PhosR in processing and generating novel biological knowledge from MS-based phosphoproteomic data.

systems biology↗

bioRxiv2018

Maternal psychosocial risk factors and offspring gestational epigenetic age acceleration in a South African birth cohort study

Epigenetic age (EA) acceleration is associated with higher risk of chronic disease and mortality in adults. However, little is known about whether and how in utero exposures might shape gestational EA acceleration at birth. We aimed to explore associations between maternal psychosocial risk factors and offspring gestational EA acceleration at birth in a South African birth cohort study - the Drakenstein Child Health Study. Maternal psychosocial risk factors included trauma/stressor exposure; posttraumatic stress disorder (PTSD); depression, psychological distress; and alcohol/tobacco use. Offspring gestational EA acceleration at birth was calculated using an epigenetic clock previously devised for neonates. Bivariate linear regression was used to explore unadjusted associations between maternal risk factors and offspring gestational EA acceleration at birth. A stepwise regression method was then used to determine the best multivariable model for adjusted associations. Data from 272 maternal-offspring dyads were included in the current analysis. In the stepwise regression model, maternal trauma exposure ({beta}=7.92; p<0.01) or PTSD ({beta}=7.46; p<0.01) were significantly associated with offspring gestational EA acceleration at birth, controlling for ethnicity, offspring sex, head circumference at birth, maternal HIV status, and prenatal tobacco or alcohol use. In site-stratified models, these associations retained statistical significance and direction of effect. Maternal trauma exposure or PTSD may thus be associated with offspring gestational EA acceleration at birth. Given the novelty of this preliminary finding, and its potential translational relevance, further studies to delineate underlying biological pathways and to explore clinical implications of EA acceleration are warranted.

genomics↗