Manuel Castro
A5032904789- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Experimental Learning in Engineering
- Computational Drug Discovery Methods
- Alzheimer's disease research and treatments
- Engineering Education and Curriculum Development
- Neuroinflammation and Neurodegeneration Mechanisms
- E-Learning and Knowledge Management
- Glycosylation and Glycoproteins Research
- Bacteriophages and microbial interactions
- Online Learning and Analytics
- Advanced Electron Microscopy Techniques and Applications
- Cell Image Analysis Techniques
- Advanced Memory and Neural Computing
- Education Pedagogy and Practices
- Higher Education Learning Practices
- Biomedical and Engineering Education
- Ion Channels and Receptors
- Biochemical Analysis and Sensing Techniques
- Fossil Insects in Amber
- Lipid Membrane Structure and Behavior
- RNA and protein synthesis mechanisms
- Education and Vocational Training
- Neurobiology and Insect Physiology Research
- Digital Economy and Work Transformation
Vanderbilt University
2018-2025
Princeton University
2020-2025
Neuroscience Institute
2020-2023
Arizona State University
2002-2020
National University of Distance Education
2006-2020
Universidad de Ciencias Medicas
2020
Institute of Electrical and Electronics Engineers
2013-2019
Bridge University
2019
Universidad de Ciencias y Humanidades
2019
Volgograd Institute of Business
2019
Abstract Understanding the brain requires understanding neurons’ functional responses to circuit architecture shaping them. Here we introduce MICrONS connectomics dataset with dense calcium imaging of around 75,000 neurons in primary visual cortex (VISp) and higher areas (VISrl, VISal VISlm) an awake mouse that is viewing natural synthetic stimuli. These data are co-registered electron microscopy reconstruction containing more than 200,000 cells 0.5 billion synapses. Proofreading a subset...
Abstract Mammalian neocortex contains a highly diverse set of cell types. These types have been mapped systematically using variety molecular, electrophysiological and morphological approaches 1–4 . Each modality offers new perspectives on the variation biological processes underlying cell-type specialization. Cellular-scale electron microscopy provides dense ultrastructural examination an unbiased perspective subcellular organization brain cells, including their synaptic connectivity...
Neural circuit function is shaped both by the cell types that comprise and connections between them1. have previously been defined morphology2,3, electrophysiology4, transcriptomic expression5,6, connectivity7-9 or a combination of such modalities10-12. The Patch-seq technique enables characterization morphology, electrophysiology properties from individual cells13-15. These were integrated to define 28 inhibitory, morpho-electric-transcriptomic (MET) in mouse visual cortex16, which do not...
We are in the era of millimetre-scale electron microscopy volumes collected at nanometre resolution1,2. Dense reconstruction cellular compartments these has been enabled by recent advances machine learning3-6. Automated segmentation methods produce exceptionally accurate reconstructions cells, but post hoc proofreading is still required to generate large connectomes that free merge and split errors. The elaborate 3D meshes neurons contain detailed morphological information multiple scales,...
Understanding the relationship between circuit connectivity and function is crucial for uncovering how brain implements computation. In mouse primary visual cortex (V1), excitatory neurons with similar response properties are more likely to be synaptically connected, but previous studies have been limited within V1, leaving much unknown about broader rules. this study, we leverage millimeter-scale MICrONS dataset analyze synaptic functional of individual across cortical layers areas. Our...
Neurons in the neocortex exhibit astonishing morphological diversity, which is critical for properly wiring neural circuits and giving neurons their functional properties. However, organizational principles underlying this diversity remain an open question. Here, we took a data-driven approach using graph-based machine learning methods to obtain low-dimensional "bar code" describing more than 30,000 excitatory mouse visual areas V1, AL, RL that were reconstructed from millimeter scale...
Abstract To understand the brain we must relate neurons’ functional responses to circuit architecture that shapes them. Here, present a large connectomics dataset with dense calcium imaging of millimeter scale volume. We recorded activity from approximately 75,000 neurons in primary visual cortex (VISp) and three higher areas (VISrl, VISal VISlm) an awake mouse viewing natural movies synthetic stimuli. The data were co-registered volumetric electron microscopy (EM) reconstruction containing...
Abstract Sensing and responding to temperature is crucial in biology. The TRPV1 ion channel a well-studied heat-sensing receptor that also activated by vanilloid compounds, including capsaicin. Despite significant interest, the molecular underpinnings of thermosensing have remained elusive. S1-S4 membrane domain couples chemical ligand binding pore during gating. Here we show significantly contributes heat-activated Evaluation isolated human solution NMR, far-UV CD, intrinsic fluorescence...
Abstract The activity and connectivity of inhibitory cells has a profound impact on the operation neuronal networks. While average many cell types been characterized, we still lack an understanding how individual interneurons distribute their synapses onto targets heterogeneous inhibition is different excitatory neurons. Here, use large-scale volumetric electron microscopy (EM) functional imaging to address this question for chandelier in layer 2/3 mouse visual cortex. Using dense...
Helical integral membrane proteins are assumed to require a lipid bilayer or model (e.g. detergent micelles) prevent aggregation and precipitation in aqueous solution. Here, we show that this is not always true single-span helical capable of forming stable but reversible protein nanoparticle assemblies (detergent-limited particles — DLPs) when purified after removal all nearly detergent. Residual DLPs exchangeable with the surrounding This work focuses on formed by transmembrane C-terminal...
Introdução: A escola é um dos principais cenários onde se manifestam, de forma clara e explícita, as dificuldades aprendizagem, que são identificadas quando o estudante não alcança mínimo aprendizado esperado, ou consegue assimilar os conteúdos pedagógicos adequados à sua faixa etária. Desse modo, a distinção entre transtornos aprendizagem fundamental, dada necessidade reconhecer estes parte do processo educacional. Objetivo: Investigar acerca das transtorno nos anos iniciais Ensino...
Introdução: O aprimoramento da liderança e gestão educacional depende do investimento no processo de formação continuada dos gestores escolares, com vista fortalecimento qualidade educação a eficiência na tomada decisões. Tal formação, quando direcionada maneira adequada, permite atualização sobre novas metodologias, políticas educacionais inovação administração escolar. Além disso, contribui para melhoria ambiente escolar aprendizado alunos. Objetivo: Compreender os principais conceitos,...
This action research aimed to enhance the graph interpretation skills of 35 Grade 9 Apitong students Baybay National High School in learning microeconomics through I2 strategy. Utilizing a mixed-methods design, study incorporated pre-and post-assessments evaluate students' skills. Quantitative data were analyzed using Wilcoxon signed-rank test assess significant differences performance, while thematic analysis was employed gain insights into experiences with The findings revealed improvement...
NMR spectroscopy has played a pivotal role in fragment-based drug discovery by coupling detection of weak ligand-target binding with structural mapping the site. Fragment-based screening been successfully applied to many soluble protein targets, but only limited number membrane proteins, despite fact that targets are proteins. This is partly because difficulties preparing proteins for NMR-especially human proteins-and inherent complexity associated solution on samples, which require...
<title>Abstract</title> The neocortex is composed of microcircuits built from distinct cell types. Despite significant progress in characterizing these types, understanding the full synaptic connections individual excitatory cells remains elusive. This study investigates connectivity arguably most well recognized neuron neocortex: thick tufted layer 5 pyramidal also known as extra telencephalic (ET) neurons using a 1 mm3 publicly available electron microscopy dataset. analysis reveals that...
This work reports substrate-selective inhibition of a protease with broad substrate specificity based on direct binding small-molecule inhibitor to the substrate. The target for these studies was γ-secretase protease, which cleaves dozens different single-span membrane protein substrates, including both C99 domain human amyloid precursor and Notch receptor. Substrate-specific cleavage is desirable reduce production amyloid-β polypeptide without inhibiting cleavage, major source toxicity...
Abstract Bacterial binding to host receptors underlies both commensalism and pathogenesis. Many streptococci adhere protein-attached carbohydrates expressed on cell surfaces using Siglec-like regions (SLBRs). The precise glycan repertoire recognized may dictate whether the organism is a strict commensal versus pathogen. However, it currently not clear what drives receptor selectivity. Here, we use five representative SLBRs identify of site that are hypervariable in sequence structure. We...
Summary The neocortex is one of the most critical structures that makes us human, and it involved in a variety cognitive functions from perception to sensory integration motor control. Composed repeated modules, or microcircuits, relies on distinct cell types as its fundamental building blocks. Despite significant progress characterizing these 1–5 , an understanding complete synaptic partners associated with individual excitatory remain elusive. Here, we investigate connectivity arguably...
The Siglec-like Serine-Rich Repeat (SRR) adhesins mediate bacterial attachment to mammalian hosts via sialoglycan receptors. Here, we combine structural, computational, biochemical, and phylogenetic approaches elucidate the determinants of sialoglycan-binding spectrum across family SRR adhesins. We further identified mutable positions that disproportionately affect selectivity, as demonstrated by increases in binding alternative ligands 2- 3-orders magnitude. Biologically, these studies...
Women in Applied Sciences and Engineering (WISE) Investments is an innovative program that introduces middle school high girls to the exciting world of engineering technology. Funded by a National Science Foundation grant, WISE seeks provide intervention at both levels showing has real applications; demonstrating problem-solving approach engineers; correcting misperceptions; providing positive information role models. Female students grades 6 through 12 were recruited commit one year where...
Abstract The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy often limited the preceding step aligning 2D to create a 3D stack. Precise and robust alignment in presence artifacts challenging, especially as datasets are attaining petascale. We present computational pipeline for ssEM with several key elements. Self-supervised convolutional nets trained via metric learning...