A5088870823- Invertebrate Immune Response Mechanisms
- Neurobiology and Insect Physiology Research
- Insect and Arachnid Ecology and Behavior
- Plant and animal studies
- Metabolism and Genetic Disorders
- Animal Behavior and Reproduction
- Physiological and biochemical adaptations
- Glycogen Storage Diseases and Myoclonus
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Carbohydrate Chemistry and Synthesis
- Muscle Physiology and Disorders
- Amino Acid Enzymes and Metabolism
- Stroke Rehabilitation and Recovery
- RNA modifications and cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Lysosomal Storage Disorders Research
- Genomic variations and chromosomal abnormalities
- Single-cell and spatial transcriptomics
- Botulinum Toxin and Related Neurological Disorders
- Neuroscience and Neuropharmacology Research
- History of Science and Natural History
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Protein Tyrosine Phosphatases
Duke University Hospital
2023-2024
Janelia Research Campus
2017-2024
University of Cambridge
2019-2024
MRC Laboratory of Molecular Biology
2024
Howard Hughes Medical Institute
2016-2024
Duke Medical Center
2022-2024
Duke University
2024
Duke University Health System
2024
Congenital Muscle Disease International Registry
2019
University of California, Irvine
2019
Abstract Molecular profiles of neurons influence neural development and function but bridging the gap between genes, circuits, behavior has been very difficult. Here we used single cell RNAseq to generate a complete gene expression atlas Drosophila larval central nervous system composed 131,077 cells across three developmental stages (1 h, 24 h 48 after hatching). We identify 67 distinct clusters based on patterns expression. These include 31 functional mature neuron clusters, 1 ring gland...
Abstract Efforts to map neural circuits have been galvanized by the development of genetic technologies that permit manipulation targeted sets neurons in brains freely behaving animals. The success these efforts relies on experimenter’s ability target arbitrarily small subsets for manipulation, but such specificity targeting cannot routinely be achieved using existing methods. In Drosophila melanogaster, a widely-used technique refined cell type-specific is Split GAL4 system, which augments...
Animal behavior is shaped both by evolution and individual experience. Parallel brain pathways encode innate learned valences of cues, but the way in which they are integrated during action-selection not well understood. We used electron microscopy to comprehensively map with synaptic resolution all neurons downstream mushroom body (MB) output (encoding valences) characterized their patterns interaction lateral horn (LH) Drosophila larva. The connectome revealed multiple convergence neuron...
Abstract Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants the two genes that encode histone H3.3 ( H3-3A / H3F3A and H3-3B H3F3B ) [1–4]. This characterized developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative de novo heterozygous either or Here, we analyze data of 58 previously published...
The mechanisms that generate neural diversity during development remains largely unknown. Here, we use scRNA-seq methodology to discover new features of the Drosophila larval CNS across several key developmental timepoints. We identify multiple progenitor subtypes - both stem cell-like neuroblasts and intermediate progenitors change gene expression development, report on candidate markers for each class progenitors. a pool quiescent in newly hatched larvae show they are transcriptionally...
Abstract Motivation As more behavioural assays are carried out in large-scale experiments on Drosophila larvae, the definitions of archetypal actions a larva regularly refined. In addition, video recording and tracking technologies constantly evolve. Consequently, automatic tagging tools for larval behaviour must be retrained to learn new representations from data. However, existing cannot transfer knowledge large amounts previously accumulated We introduce LarvaTagger, piece software that...
To better characterize adult myotubularin 1 (MTM1)-related myopathy carriers and recommend a phenotypic classification.This cohort study was performed at the NIH Clinical Center. Participants were required to carry confirmed MTM1 mutation recruited via Congenital Muscle Disease International Registry (n = 8), traveling local clinic of Neuromuscular Neurogenetic Disorders Childhood Section, National Institute Neurological Stroke, Cure CMD 1), direct physician referral 1). examinations, muscle...
Abstract Animal behavior is shaped both by evolution and individual experience. In many species parallel brain pathways are thought to encode innate learnt drives as a result may link the same sensory cue different actions if in opposition. How these opposing integrated into single coherent action not well understood. insects, Mushroom Body Output Neurons (MBONs) Lateral Horn (LHNs) provide drives, respectively. However their patterns of convergence mechanisms which outputs used select We...
Summary Molecular profiles of neurons influence information processing, but bridging the gap between genes, circuits, and behavior has been very difficult. Furthermore, behavioral state an animal continuously changes across development as a result sensory experience. How influences molecular cell is poorly understood. Here we present complete atlas Drosophila larval central nervous system composed over 200,000 single cells four developmental stages. We develop polyseq , python package, to...
Biallelic loss-of-function variants in the MUSK gene result two allelic disorders: (1) congenital myasthenic syndrome (CMS; OMIM: 616325), a neuromuscular disorder that has range of severity from severe neonatal-onset weakness to mild adult-onset weakness, and (2) fetal akinesia deformation sequence (OMIM: 208150), form pregnancy loss characterized by muscle fetus. The codes for muscle-specific kinase (MuSK), receptor tyrosine involved development junction. Here, we report case MUSK-related...
Abstract The central nervous system can generate various behaviours, including motor responses, which we observe through video recordings. Recent advancements in genetics, automated behavioural acquisition at scale, and machine learning enable us to link behaviours their underlying neural mechanisms causally. Moreover, some animals, such as the Drosophila larva, this mapping is possible unprecedented scales of millions animals single neurons, allowing identify circuits generating particular...
We present semiparametric spectral modeling of the complete larval Drosophila mushroom body connectome. Motivated by a thorough exploratory data analysis network via Gaussian mixture (GMM) in adjacency embedding (ASE) representation space, we introduce latent structure model (LSM) for and inference. LSM is generalization stochastic block (SBM) special case random dot product graph (RDPG) position model, amenable to GMM ASE space. The resulting connectome code derived composed with captures...
Rapid genome sequencing in critically ill infants is increasingly identified as a crucial test for providing targeted and informed patient care. We report the outcomes of pilot study wherein eight neonates received rapid whole with parental samples an effort to establish prompt diagnosis. Our resulted 37.5% diagnostic rate by alone overall 50% cohort. describe how diagnoses led identification additional affected relatives change management, limitations sequencing, some challenges sample...
Muscle strength testing is routine in clinical practice. Here we provide an aid to the documentation and visual conceptualization of those results - MuscleViz: a free, open-source application for visualizing muscle testing. Its use settings streamlines communication physical examination findings. The tool also useful presenting patient data case reports or series. A push towards software has benefitted other areas science; believe similar effort dedicated development tools worth pursuing.
Galactosemia is an inborn error of galactose metabolism caused by mutations in the GALT gene. Though early detection and restriction prevent severe liver disease, affected individuals have persistently elevated biomarkers often neuro-developmental symptoms. We present a teenage compound heterozygote for known pathogenic mutation (H132Q) novel variant unknown significance (S222N), with nearly absent erythrocyte enzyme activity but normal only mild anxiety despite diet non-adherence. This case...