Jeremy W. Linsley
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View article: A dynamic in vitro model of Down syndrome neurogenesis with trisomy 21 gene dosage correction
A dynamic in vitro model of Down syndrome neurogenesis with trisomy 21 gene dosage correction Open
Excess gene dosage from chromosome 21 (chr21) causes Down syndrome (DS), spanning developmental and acute phenotypes in terminal cell types. Which phenotypes remain amenable to intervention after development is unknown. To address this que…
View article: Three dimensional and four dimensional live imaging to study mechanisms of progressive neurodegeneration
Three dimensional and four dimensional live imaging to study mechanisms of progressive neurodegeneration Open
View article: A deep-learning-based screening platform in aging-relevant human motor neurons to identify therapeutic compounds for amyotrophic lateral sclerosis
A deep-learning-based screening platform in aging-relevant human motor neurons to identify therapeutic compounds for amyotrophic lateral sclerosis Open
Age is the primary risk factor for most neurodegenerative diseases including amyo-trophic lateral sclerosis (ALS). Despite the clear importance of age on the development and progression of ALS, age is rarely considered a factor in cellular…
View article: Neural scaling laws for phenotypic drug discovery
Neural scaling laws for phenotypic drug discovery Open
Recent breakthroughs by deep neural networks (DNNs) in natural language processing (NLP) and computer vision have been driven by a scale-up of models and data rather than the discovery of novel computing paradigms. Here, we investigate if …
View article: Stac1 Regulates Sensory Stimulus Induced Escape Locomotion
Stac1 Regulates Sensory Stimulus Induced Escape Locomotion Open
The stac family of genes are expressed by several cell types including neurons and muscles in a wide variety of animals. In vertebrates, stac3 encodes an adaptor protein specifically expressed by skeletal muscle that regulates L-type calci…
View article: Fluorescently labeled nuclear morphology is highly informative of neurotoxicity
Fluorescently labeled nuclear morphology is highly informative of neurotoxicity Open
Neurotoxicity can be detected in live microscopy by morphological changes such as retraction of neurites, fragmentation, blebbing of the neuronal soma and ultimately the disappearance of fluorescently labeled neurons. However, quantificati…
View article: A dynamic<i>in vitro</i>model of Down Syndrome neurogenesis with Trisomy 21 gene dosage correction
A dynamic<i>in vitro</i>model of Down Syndrome neurogenesis with Trisomy 21 gene dosage correction Open
/SUMMARY Excess gene dosage from human chromosome 21 (chr21) causes Down syndrome (DS), spanning developmental as well as acute phenotypes in terminal cell types. Which phenotypes remain amenable to intervention after development is unknow…
View article: Superhuman cell death detection with biomarker-optimized neural networks
Superhuman cell death detection with biomarker-optimized neural networks Open
High-throughput microscopy has outpaced analysis; biomarker-optimized CNNs are a generalizable, fast, and interpretable solution.
View article: Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration
Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration Open
View article: Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration
Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration Open
Cell death is a critical process that occurs normally in health and disease. However, its study is limited due to available technologies that only detect very late stages in the process or specific death mechanisms. Here, we report the dev…
View article: Stac protein regulates release of neuropeptides
Stac protein regulates release of neuropeptides Open
Significance Many neurons release neuropeptides as well as classical neurotransmitters. Neuropeptides often regulate neural circuits controlling behaviors such as emotional behaviors. However, how neuropeptide release is regulated is not w…
View article: Stac3 is a component of the excitation–contraction coupling machinery and mutated in Native American myopathy
Stac3 is a component of the excitation–contraction coupling machinery and mutated in Native American myopathy Open
Excitation-contraction coupling, the process that regulates contractions by skeletal muscles, transduces changes in membrane voltage by activating release of Ca2+ from internal stores to initiate muscle contraction. Defects in EC coupling …
View article: Dstac Regulates Excitation-Contraction Coupling in Drosophila Body Wall Muscles
Dstac Regulates Excitation-Contraction Coupling in Drosophila Body Wall Muscles Open
Stac3 regulates excitation-contraction coupling (EC coupling) in vertebrate skeletal muscles by regulating the L-type voltage-gated calcium channel (Cav channel). Recently a stac-like gene, Dstac, was identified in…
View article: Single cell tracking based on Voronoi partition via stable matching
Single cell tracking based on Voronoi partition via stable matching Open
Live-cell imaging is an important technique to study cell migration and proliferation as well as image-based profiling of drug perturbations over time. To gain biological insights from live-cell imaging data, it is necessary to identify in…
View article: Super-human cell death detection with biomarker-optimized neural networks
Super-human cell death detection with biomarker-optimized neural networks Open
Cell death is an essential process in biology that must be accounted for in live microscopy experiments. Nevertheless, cell death is difficult to detect without perturbing experiments with stains, dyes or biosensors that can bias experimen…
View article: Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration
Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration Open
Cell death is a critical process that occurs normally in health and disease. However, its study is limited due to available technologies that only detect very late stages in the process or specific death mechanisms. Here, we report the dev…
View article: Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD
Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD Open
View article: Cell death assays for neurodegenerative disease drug discovery
Cell death assays for neurodegenerative disease drug discovery Open
Introduction: Neurodegenerative diseases affect millions of people worldwide. Neurodegeneration is gradual over time, characterized by neuronal death that causes deterioration of cognitive or motor functions, ultimately leading to t…
View article: Automated four-dimensional long term imaging enables single cell tracking within organotypic brain slices to study neurodevelopment and degeneration
Automated four-dimensional long term imaging enables single cell tracking within organotypic brain slices to study neurodevelopment and degeneration Open
View article: <i>Dstac</i>is required for normal circadian activity rhythms in<i>Drosophila</i>
<i>Dstac</i>is required for normal circadian activity rhythms in<i>Drosophila</i> Open
The genetic, molecular and neuronal mechanism underlying circadian activity rhythms is well characterized in the brain of Drosophila. The small ventrolateral neurons (s-LNVs) and pigment dispersing factor (PDF) expressed by them…
View article: Transport of the alpha subunit of the voltage gated L‐type calcium channel through the sarcoplasmic reticulum occurs prior to localization to triads and requires the beta subunit but not Stac3 in skeletal muscles
Transport of the alpha subunit of the voltage gated L‐type calcium channel through the sarcoplasmic reticulum occurs prior to localization to triads and requires the beta subunit but not Stac3 in skeletal muscles Open
Contraction of skeletal muscle is initiated by excitation‐contraction ( EC ) coupling during which membrane voltage is transduced to intracellular Ca 2+ release. EC coupling requires L‐type voltage gated Ca 2 + channels (the dihydropyridin…
View article: Congenital myopathy results from misregulation of a muscle Ca <sup>2+</sup> channel by mutant Stac3
Congenital myopathy results from misregulation of a muscle Ca <sup>2+</sup> channel by mutant Stac3 Open
Significance Skeletal muscle contractions are regulated by a process called excitation–contraction (EC) coupling, and defects in it are associated with numerous human myopathies. Recently, stac3 (SH3 and cysteine-rich domain 3) was identif…