Biology subjects

Smith, R. M.

Publications and source records attributed to Smith, R. M..

9 recordsLinked to original sources

bioRxiv2026

Draft genome assembly of the Woolly bottlebrush (Greyia radlkoferi) using Pacbio long-read sequencing technology.

The Woolly bottlebrush (Greyia radlkoferi) is an indigenous South African plant known for its ornamental appeal and potential medicinal uses. It naturally grows on rocky hillsides and grasslands and highly resilient to drought, temperature fluctuations, and nutrient-poor soils. Its flavonoid-rich compounds with anti-tyrosinase activity support its traditional use to treat skin pigmentation disorders in humans. Despite its outstanding ecological and biochemical characteristics, no reference genome is available for Greyia radlkoferi. Therefore, this study aimed to generate the first draft genome of the Greyia Radlkofleri using PacBio Sequel IIe HiFi long read sequencing. A total of 56.07 Gb HiFi data was generated, providing a total genome coverage of 270X. The assembled genome size was 206Mb, with the longest scaffold being 13.9 Mb. The assembly statistics yielded a scaffold and contig N50 of 10.1 Mb, and an L50 of 9, and with an overall GC content of 34.9 %. The genome scope profile set at kmer = 17 indicated that the genome is triploid. The genome annotation predicted 17,804 protein-coding genes and 17,804 transcripts with an average gene length of 3,116.03 bp. This is the first draft genome of its kind for the Greyia genus and provides a foundation for future studies aimed at elucidating the genetic basis of its environmental resilience and the biosynthetic pathways underlying its medicinal properties.

genomics↗

bioRxiv2026

Skin DNA Methylation Encodes Multidimensional Facial Aging Phenotypes with Distinct Biological Architectures

Whether distinct visible aging traits, e.g., wrinkling, pigmentation, and inflammation, reflect shared or independent epigenetic programs remains unknown; existing clocks compress aging into a single chronological axis, leaving the phenotype-specific architecture of cutaneous aging uncharacterized. Here, we integrate AI-derived facial phenotypes with skin DNA methylation profiles from 706 individuals to develop EpiVision, a panel of 21 epigenetic predictors spanning structural, pigmentary, inflammatory, and textural aging traits. Predictors reveal shared and trait-specific pathways, including developmental patterning, epithelial remodeling, hormonal signaling, and UV damage responses, and capture environmentally induced acceleration in sun-exposed skin alongside lifestyle and topical treatment-associated variation. These findings establish that visible skin aging comprises molecularly distinct axes with shared regulatory substrates and trait-specific drivers, providing a scalable epigenetic framework for intervention evaluation and aging biology research.

genomics↗

bioRxiv2026

Chromosome-level Genome Assembly of the South African Lion (Panthera leo melanochaita)

The lion (Panthera leo melanochaita) is one of the most iconic species and part of the big five, maintaining ecological balance and a major wildlife-based tourism attraction in South Africa. Despite its importance, it is currently threatened by rapid population decline and increasing population fragmentation. Therefore, there is a need for a high-quality genomic resource that captures the diverse genetic landscape of South African lion populations. To address this, we present a high-quality genome assembly of the lion, generated using PacBio HiFi and Omni-C sequencing technologies. The final assembly comprises 2.45 Gb, with a scaffold N50 of 148 Mb and a contig N50 of 22 Mb. Remarkably, 94.8% of the genome is anchored to 19 scaffolds, reflecting the high degree of contiguity and near-complete chromosomal level. Completeness assessment of the genome showed 98.2% BUSCO, 98.2% k-mer completeness and QV of 65.6 underscoring high accuracy and biological integrity. Genome annotation predicted 831.4 Mb (33.9%) of repetitive sequences and 21 739 protein-coding genes. This work provides high-quality genomic resource to establish a foundation for future population genomic and conservation-focused investigations of the lion populations in South Africa.

genomics↗

bioRxiv2025

Chromosome-Level Genome Assembly of Southern Africa Mozambique Tilapia (Oreochromis mossambicus) using PacBio HiFi and Omni-C sequencing

The Mozambique tilapia (Oreochromis mossambicus) is a species of significant ecological and economic importance in Southern Africa. However, urbanization and water management challenges have led to the species being classified as threatened by the International Union for Conservation of Nature. Despite its widespread distribution and significance as a key food source, the genetic architecture of Southern African O. mossambicus remains inadequately characterized. This gap in knowledge hinders efforts to conserve and manage the species effectively. This study presents a high-quality chromosome-level genome assembly for a South African O. mossambicus assembled using both PacBio HiFi and Dovetail Omni-C sequencing. The 1.09 Gb assembly is highly contiguous, with 99.4% of sequences anchored into 22 chromosomes and a BUSCO completeness of 99.5%. We annotated 27,544 protein-coding genes. This genome provides an essential resource for preserving native biodiversity and enabling genomic selection for traits like disease resistance and growth performance within the South African aquaculture context.

genomics↗

bioRxiv2025

A chromosome-level genome assembly of the South African indigenous, Kolbroek pig, Sus scrofa domesticus

The Kolbroek pig is indigenous to South Africa and a breed of choice for smallholder farmers. This is mainly due to its characteristics, such as disease resistance and adaptability to tropical agroecological environments. Despite these desirable traits, the genomic architecture of this breed has not been explored. In this study, we report a high-quality genome assembly of the South African Kolbroek pig sequenced at 31 x coverage through a combination of PacBio Sequel IIe HiFi and Illumina Novaseq 6000 Omni-C sequencing. The assembled genome resulted in a length of 2.6 Gb in size, including 83 Scaffolds, which consist of 19 chromosome-size scaffolds with 138.7 Mb/48.5 Mb for scaffold/contig N50 respectively. The BUSCO completeness at 95.5 %. Genome annotation and structure prediction identified 22,025 genes with protein-coding potential. The genome provides an opportunity to investigate genetic variation across multiple pig breeds and serves as a genetic resource to develop breeding programs for the conservation and improvement of the Kolbroek pig.

genomics↗

bioRxiv2023

Effects of menopause and high fat diet on metabolic outcomes in a mouse model of Alzheimer's disease.

About two-thirds of those with Alzheimers disease (AD) are women, most of whom are post-menopausal. Menopause accelerates the risk for dementia by increasing the risk for metabolic, cardiovascular, and cerebrovascular diseases. Mid-life metabolic disease (e.g. obesity, diabetes, or prediabetes) is a well-known risk factor for dementia. A high fat diet can lead to poor metabolic health in both humans and rodents. The goal of this study was to determine the effects of menopause and high fat diet on metabolic outcomes in the AppNL-F knock-in mouse model of Alzheimers disease. To model menopause, we used an accelerated ovarian failure model (4-vinylcyclohexene diepoxide, VCD). This ovary-intact model is more clinically relevant than an ovariectomy model, as mice go through a perimenopausal period. At 3 months of age, AppNL-F mice were administered VCD or vehicle (oil) and then placed on either a control diet (10% fat) or a high fat diet (HF; 60% fat) and maintained on the diets until 10 months of age. Menopause led to metabolic impairment (weight gain and glucose intolerance) and further exacerbated obesity in response to a high fat diet. Menopause had independent effects on some serum metabolic health biomarkers (insulin) and synergic effects with HF diet on other markers (glucagon). Some metabolic effects of menopause may be centrally mediated, as menopause altered the expression of hypothalamic genes related to energy balance and increased microgliosis in the lateral hypothalamic nucleus. This work highlights the need to model endocrine aging in animal models of dementia and will contribute to further understanding the interaction between menopause and metabolic health in the context of AD. HighlightsO_LIIn a mouse model of AD, menopause, modeled by accelerated ovarian failure, leads to metabolic impairment. C_LIO_LIMenopause has independent effects on some serum metabolic health biomarkers (insulin) and synergic effects with HF diet on other markers (glucagon). C_LIO_LIMenopause alters the expression of hypothalamic energy balance related genes. C_LIO_LIMenopause leads to increased microgliosis in the lateral hypothalamic nucleus. C_LI

neuroscience↗

bioRxiv2023

Brain Specific Estrogen Ameliorates Cognitive Effects of Surgical Menopause in Mice

Menopause is a major endocrinological shift that leads to an increased vulnerability to the risk factors for cognitive impairment and dementia. This is thought to be due to the loss of circulating estrogens, which exert many potent neuroprotective effects in the brain. Systemic replacement of estrogen post-menopause has many limitations, including increased risk for estrogen-sensitive cancers. A more promising therapeutic approach therefore might be to deliver estrogen only to the brain thus limiting adverse peripheral side effects. We examined whether we could enhance cognitive performance by delivering estrogen exclusively to the brain in post-menopausal mice. We modeled surgical menopause via bilateral ovariectomy (OVX). We treated mice with the pro-drug 10{beta},17{beta}-dihydroxyestra-1,4-dien-3-one (DHED), which can be administered systemically but is converted to 17{beta}-estradiol only in the brain. Young (2.5-month) and middle-aged (11-month-old) female C57BL/6J mice received ovariectomy and a subcutaneous implant containing vehicle (cholesterol) or DHED. At 3.5 months old (young group) and 14.5 months old (middle-aged group), mice underwent behavior testing to assess memory. DHED did not significantly alter metabolic status in middle-aged, post-menopausal mice. In both young and middle-aged mice, the brain-specific estrogen DHED improved spatial memory. Additional testing in middle-aged mice also showed that DHED improved working and recognition memory. These promising results lay the foundation for future studies aimed at determining if this intervention is as efficacious in models of dementia that have comorbid risk factors.

neuroscience↗

bioRxiv2021

Vestibular Agnosia is linked to abnormal functional brain networks

Vestibular Agnosia - where peripheral vestibular activation triggers the usual reflex nystagmus response but with attenuated or no self-motion perception - is found in brain disease with disrupted cortical network functioning, e.g. traumatic brain injury (TBI) or neurodegeneration (Parkinsons Disease). Patients with acute focal hemispheric lesions (e.g. stroke) do not manifest vestibular agnosia. Thus brain network mapping techniques, e.g. resting state functional MRI (rsfMRI), are needed to interrogate functional brain networks mediating vestibular agnosia. Whole-brain rsfMRI was acquired from 39 prospectively recruited acute TBI patients with preserved peripheral vestibular function, along with self-motion perceptual thresholds during passive yaw rotations in the dark. Following quality-control checks, 25 patient scans were analyzed. TBI patients were classified as having vestibular agnosia (n = 11) or not (n = 14) via laboratory testing of self-motion perception. Using independent component analysis, we found altered functional connectivity in the right superior longitudinal fasciculus and left rostral prefrontal cortex in vestibular agnosia. Moreover, regions of interest analyses showed both inter-hemispheric and intra-hemispheric network disruption in vestibular agnosia. In conclusion, our results show that vestibular agnosia is mediated by bilateral anterior and posterior network dysfunction and reveal the distributed brain mechanisms mediating vestibular self-motion perception.

neuroscience↗

bioRxiv2019

Vascular endothelial growth factor (VEGF) expression and neuroinflammation is increased in the frontopolar cortex of individuals with autism spectrum disorder

Autism spectrum disorder (ASD) etiology is a complex mixture of genetic and environmental factors, the relative contributions of which varies across patients. Despite complex etiology, researchers observe consistent neurodevelopmental features in ASD patients, notably atypical forebrain cortical development. Growth factors, cytokines, and chemokines are important mediators of forebrain cortical development, but have not been thoroughly examined in brain tissues from individuals with autism. Here, we performed an integrative analysis of RNA and protein expression using frontopolar cortex tissues dissected from individuals with ASD and controls, hypothesizing that ASD patients will exhibit aberrant expression of growth factors, cytokines, and chemokines critical for neurodevelopment. We performed group-wise comparisons of RNA expression via RNA-Seq and growth factor, cytokine, and chemokine expression via multiplex enzyme-linked immunosorbent assay (ELISA). We also analyzed single cell sequencing data from the frontopolar cortex of typically developed individuals to identify cell types that express the growth factors we found differentially expressed in ASD. Our RNA-Seq analysis revealed 11 differentially expressed genes in ASD versus control brains, the most significant of which encodes for vascular endothelial growth factor (VEGF-A). Both RNA and protein levels of VEGF-A were upregulated in ASD brains. Our single cell analysis revealed that VEGF is expressed primarily by non-neuronal cells. We also found that the differentially expressed genes from our RNA-Seq analysis are enriched in microglia. The increased VEGF-A expression we observed in ASD, coupled with the enrichment of differentially expressed genes in microglia, begs the question of the role VEGF-A is playing in ASD. Microglia activation, as indicated by our RNA-Seq results, and the VEGF-A isoform expression we see in the ASD cortex, leads us to conclude that VEGF-A is playing a pro-inflammatory role, perhaps with unwanted long-term consequences for neurodevelopment.

genomics↗