A5024099929- Neonatal and fetal brain pathology
- Advanced Neuroimaging Techniques and Applications
- Neonatal Respiratory Health Research
- Infant Development and Preterm Care
- Fetal and Pediatric Neurological Disorders
- Functional Brain Connectivity Studies
- Maternal Mental Health During Pregnancy and Postpartum
- Microtubule and mitosis dynamics
- Genetics and Neurodevelopmental Disorders
- Epilepsy research and treatment
- Birth, Development, and Health
- Stress Responses and Cortisol
- Tracheal and airway disorders
- Epigenetics and DNA Methylation
- Preterm Birth and Chorioamnionitis
- Cerebral Palsy and Movement Disorders
- Infant Nutrition and Health
- Cystic Fibrosis Research Advances
- Neural dynamics and brain function
- Radiation Dose and Imaging
- DNA Repair Mechanisms
- Pharmacological Effects and Toxicity Studies
- Nuclear Structure and Function
- Genetic and Kidney Cyst Diseases
- Infant Health and Development
Royal Hospital for Children
2016-2024
NHS Lothian
2017-2024
Royal Edinburgh Hospital
2023
Royal Hospital for Sick Children
2017-2022
Aberdeen Royal Infirmary
2013-2014
NHS Grampian
2013-2014
University of Toronto
2010
University of Tennessee Health Science Center
1969
Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct form cell type– and context-specific microtubule structures is poorly understood. Based on a cohort 12 patients with primary ciliary dyskinesia as well mouse mutants, we identified characterized variants TUBB4B isotype that specifically perturbed centriole cilium biogenesis. Distinct differentially affected dynamics cilia formation...
Compaction of chromosomes is essential for accurate segregation the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance mitotic structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits these complexes, cause microcephaly. addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed...
Preterm infants are at increased risk of alterations in brain structure and connectivity, subsequent neurocognitive impairment. Breast milk may be more advantageous than formula feed for promoting development born term, but uncertainties remain about its effect on preterm the optimal nutritional regimen infants. We test hypothesis that breast exposure is associated with improved markers connectivity term equivalent age. collected information neonatal MRI age from 47 (mean postmenstrual [PMA]...
Methadone is used for medication-assisted treatment of heroin addiction during pregnancy. The neurodevelopmental outcome children with prenatal methadone exposure can be sub-optimal. We tested the hypothesis that brain development altered among newborn infants whose mothers were prescribed methadone. 20 methadone-exposed neonates born after 37 weeks' postmenstrual age (PMA) and non-exposed controls underwent diffusion MRI at mean PMA 39+ 2 41+ 1 weeks, respectively. An age-optimized...
Gillespie syndrome (GS) is characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, and progressive cerebellar atrophy. Trio-based exome sequencing identified de novo mutations in ITPR1 three unrelated individuals with GS recruited to the Deciphering Developmental Disorders study. Whole-exome or targeted sequence analysis plausible disease-causing 10/10 additional GS-affected individuals. These ultra-rare protein-altering variants affected only residues...
Multi-contrast MRI captures information about brain macro- and micro-structure which can be combined in an integrated model to obtain a detailed "fingerprint" of the anatomical properties individual's brain. Inter-regional similarities between features derived from structural diffusion MRI, including regional volumes, tensor metrics, neurite orientation dispersion density imaging measures, modelled as morphometric similarity networks (MSNs). Here, individual MSNs were 105 neonates (59...
Preterm birth is closely associated with diffuse white matter dysmaturation inferred from diffusion MRI and neurocognitive impairment in childhood. Diffusion tensor imaging (DTI) neurite orientation dispersion density (NODDI) are distinct dMRI modalities, yet metrics derived these two methods share variance across tracts. This raises the hypothesis that dimensionality reduction approaches may provide efficient whole-brain estimates of microstructure capture (dys)maturational processes. To...
Abstract Preterm birth is associated with dysconnectivity of structural brain networks and a leading cause neurocognitive impairment in childhood. Variation DNA methylation early exposure to extrauterine life but there has been little research exploring its relationship development. Using genome-wide data from the saliva 258 neonates, we investigated impact gestational age on methylome performed functional analysis identify enriched gene sets probes that contributed differentially methylated...
Preterm birth is closely associated with a phenotype that includes brain dysmaturation and neurocognitive impairment, commonly termed Encephalopathy of Prematurity (EoP), which systemic inflammation considered key driver. DNA methylation (DNAm) signatures from peripheral blood associate poor imaging outcomes in adult cohorts. However, the robustness DNAm inflammatory scores infancy, their relation to comorbidities preterm characterised by inflammation, neonatal neuroimaging metrics EoP,...
Importance Preterm birth and socioeconomic status (SES) are associated with brain structure in childhood, but the relative contributions of each during neonatal period unknown. Objective To investigate associations gestational age (GA) SES morphology by testing 3 hypotheses: GA morphology; between vary GA; depend on how is operationalized. Design, Setting, Participants This cohort study recruited participants from November 2016 to September 2021 at a single center United Kingdom. were 170...
The mechanisms linking maternal stress in pregnancy with infant neurodevelopment a sexually dimorphic manner are poorly understood. We tested the hypothesis that hypothalamic-pituitary-adrenal axis activity, measured by hair cortisol concentration (HCC), is associated microstructure, structural connectivity, and volume of amygdala. In 78 mother-infant dyads, was sampled postnatally, infants underwent magnetic resonance imaging at term-equivalent age. found relationship between HCC amygdala...
Lamins are the major component of nuclear lamina, maintaining structural integrity nucleus. Lamin A/C variants well established to cause a spectrum disorders ranging from myopathies progeria, termed laminopathies. Phenotypes resulting in LMNB1 and LMNB2 have been much less clearly defined.
Objective Breast milk exposure is associated with improved neurocognitive outcomes following preterm birth but the neural substrates linking breast outcome are uncertain. We tested hypothesis that high versus low in infants results cortical morphology more closely resembles of term‐born infants. Methods studied 135 (<32 weeks’ gestation) and 77 term Feeding data were collected from until hospital discharge brain magnetic resonance imaging (MRI) was performed at term‐equivalent age....
The early life environment programmes cortical architecture and cognition across the course. A measure of organisation that integrates information from multimodal MRI is unbound by arbitrary parcellations has proven elusive, which hampers efforts to uncover perinatal origins health. Here, we use Vogt-Bailey index provide a fine-grained description regional homogeneities sharp variations in microstructure based on feature gradients, investigate impact being born preterm development at...
Acute appendicitis is a common surgical emergency in the paediatric population. Computed tomography (CT) has been shown to have high accuracy and low operator dependence diagnosis of appendicitis. However, with increased concerns regarding CT usage children, ultrasound (US) imaging modality choice patients where suspected. This review describes illustrates step-wise graded-compression technique for visualisation appendix, normal pathological appearances as well characteristics...
Preterm birth is associated with dysconnectivity of structural brain networks, impaired cognition and psychiatric disease. Systemic inflammation contributes to cerebral dysconnectivity, but the immune mediators driving this association are poorly understood. We analysed information from placenta, umbilical cord neonatal blood, MRI determine which link perinatal systemic networks.Participants were 102 preterm infants (mean gestational age 29+1 weeks, range 23+3-32+0). Placental histopathology...
Preterm birth is closely associated with cognitive impairment and generalized dysconnectivity of neural networks inferred from water diffusion MRI (dMRI) metrics. Peak width skeletonized mean diffusivity (PSMD) a metric derived histogram analysis across the white matter skeleton, it useful biomarker cognition in adulthood. We calculated PSMD five other based metrics tensor imaging (DTI) neurite orientation dispersion (NODDI) newborn, evaluated their accuracy as biomarkers microstructural...
DNA replication is fundamental for cell proliferation in all organisms. Nonetheless, components of the replisome have been implicated human disease, and here we report PRIM1 encoding catalytic subunit primase as a novel disease gene. Using variant classification agnostic approach, biallelic mutations were identified five individuals. protein levels markedly reduced patient cells, accompanied by fork asymmetry, increased interorigin distances, stress, prolonged S-phase duration. Consequently,...
Abstract The human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the range of functional specializations in brain. emergence this hierarchical complexity development is unknown. Here, we substantiate tiers and brain networks newborn period, assess correspondences adulthood, investigate effect preterm birth, leading cause atypical later neurocognitive impairment, on complexity. We report that neonatal connectomes are both composed...