A novel method for clustering cellular data to improve classification.

Many fields, such as neuroscience, are experiencing the vast proliferation of cellular data, underscoring the need for organizing and interpreting large datasets. A popular approach partitions data into manageable subsets via hierarchical clustering, but objective methods to determine the appropriate classification granularity are missing. We recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within clusters.

A Novel Method for Clustering Cellular Data to Improve Classification.

Many fields, such as neuroscience, are experiencing the vast proliferation of cellular data, underscoring the need for organizing and interpreting large datasets. A popular approach partitions data into manageable subsets via hierarchical clustering, but objective methods to determine the appropriate classification granularity are missing. We recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within clusters.

Hippocampome.org 2.0 is a knowledge base enabling data-driven spiking neural network simulations of rodent hippocampal circuits.

Hippocampome.org is a mature open-access knowledge base of the rodent hippocampal formation focusing on neuron types and their properties. Previously, Hippocampome.

Automatic identification of scientific publications describing digital reconstructions of neural morphology.

The increasing number of peer-reviewed publications constitutes a challenge for biocuration. For example, NeuroMorpho.Org, a sharing platform for digital reconstructions of neural morphology, must evaluate more than 6000 potentially relevant articles per year to identify data of interest.

Structural Analysis of Mitochondria in Cardiomyocytes: Insights into Bioenergetics and Membrane Remodeling.

Mitochondria in mammalian cardiomyocytes display considerable structural heterogeneity, the significance of which is not currently understood. We use electron microscopic tomography to analyze a dataset of 68 mitochondrial subvolumes to look for correlations among mitochondrial size and shape, crista morphology and membrane density, and organelle location within rat cardiac myocytes. A tomographic analysis guided the definition of four classes of crista morphology: lamellar, tubular, mixed and transitional, the last associated with remodeling between lamellar and tubular cristae.

Hippocampome.org v2.0: a knowledge base enabling data-driven spiking neural network simulations of rodent hippocampal circuits.

Hippocampome.org is a mature open-access knowledge base of the rodent hippocampal formation focusing on neuron types and their properties. Hippocampome.

Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modelling.

Schizophrenia phenotypes are suggestive of impaired cortical plasticity in the disease, but the mechanisms of these deficits are unknown. Genomic association studies have implicated a large number of genes that regulate neuromodulation and plasticity, indicating that the plasticity deficits have a genetic origin. Here, we used biochemically detailed computational modelling of post-synaptic plasticity to investigate how schizophrenia-associated genes regulate long-term potentiation (LTP) and depression (LTD).

Neuronal Connectivity as a Determinant of Cell Types and Subtypes.

Classifications of single neurons at brain-wide scale is a powerful way to characterize the structural and functional organization of a brain. We acquired and standardized a large morphology database of 20,158 mouse neurons, and generated a whole-brain scale potential connectivity map of single neurons based on their dendritic and axonal arbors. With such an anatomy-morphology-connectivity mapping, we defined neuron connectivity types and subtypes (both called "c-types" for simplicity) for neurons in 31 brain regions.

BigNeuron: a resource to benchmark and predict performance of algorithms for automated tracing of neurons in light microscopy datasets.

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms.

Local Microtubule and F-Actin Distributions Fully Constrain the Spatial Geometry of Sensory Dendritic Arbors.

Dendritic morphology underlies the source and processing of neuronal signal inputs. Morphology can be broadly described by two types of geometric characteristics. The first is dendrogram topology, defined by the length and frequency of the arbor branches; the second is spatial embedding, mainly determined by branch angles and straightness.

The Zinc-BED Transcription Factor Bedwarfed Promotes Proportional Dendritic Growth and Branching through Transcriptional and Translational Regulation in .

Dendrites are the primary points of sensory or synaptic input to a neuron and play an essential role in synaptic integration and neural function. Despite the functional importance of dendrites, relatively less is known about the underlying mechanisms regulating cell type-specific dendritic patterning. Herein, we have dissected the functional roles of a previously uncharacterized gene, , in cell type-specific dendritic development in .

The Zinc-BED transcription factor Bedwarfed promotes proportional dendritic growth and branching through transcriptional and translational regulation in .

Dendrites are the primary points of sensory or synaptic inputs to a neuron and play an essential role in synaptic integration and neural function. Despite the functional importance of dendrites, relatively less is known about the underlying mechanisms regulating cell-type specific dendritic patterning. Herein, we have dissected functional roles of a previously uncharacterized gene, , in cell-type specific dendritic development in .

Automatic identification of scientific publications describing digital reconstructions of neural morphology.

Motivation: The increasing number of peer-reviewed publications constitutes a challenge for biocuration. For example, NeuroMorpho.Org, a sharing platform for digital reconstructions of neural morphology, must evaluate more than 6000 potentially relevant articles per year to identify data of interest.

PP2A phosphatase regulates cell-type specific cytoskeletal organization to drive dendrite diversity.

Uncovering molecular mechanisms regulating dendritic diversification is essential to understanding the formation and modulation of functional neural circuitry. Transcription factors play critical roles in promoting dendritic diversity and here, we identify PP2A phosphatase function as a downstream effector of Cut-mediated transcriptional regulation of dendrite development. Mutant analyses of the PP2A catalytic subunit () or the scaffolding subunit ( reveal cell-type specific regulatory effects with the PP2A complex required to promote dendritic growth and branching in Class IV (CIV) multidendritic (md) neurons, whereas in Class I (CI) md neurons, PP2A functions in restricting dendritic arborization.

Molecular Dynamics Simulations to Decipher the Role of Phosphorylation of SARS-CoV-2 Nonstructural Proteins (nsps) in Viral Replication.

Protein phosphorylation is a post-translational modification that enables various cellular activities and plays essential roles in protein interactions. Phosphorylation is an important process for the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To shed more light on the effects of phosphorylation, we used an ensemble of neural networks to predict potential kinases that might phosphorylate SARS-CoV-2 nonstructural proteins (nsps) and molecular dynamics (MD) simulations to investigate the effects of phosphorylation on nsps structure, which could be a potential inhibitory target to attenuate viral replication.

Assisted neuroscience knowledge extraction via machine learning applied to neural reconstruction metadata on NeuroMorpho.Org.

The amount of unstructured text produced daily in scholarly journals is enormous. Systematically identifying, sorting, and structuring information from such a volume of data is increasingly challenging for researchers even in delimited domains. Named entity recognition is a fundamental natural language processing tool that can be trained to annotate, structure, and extract information from scientific articles.

Impaired rate-dependent depression of the H-reflex in type-2 diabetes, prediabetes, overweight and obesity: A cross-sectional study.

Type-2 diabetes is a chronic metabolic disorder characterized by hyperglycemia, resulting from deficits in insulin secretion or insulin resistance. According to the International Diabetes Federation, approximately 463 million people suffered from this condition in 2019, with a rapidly increasing impact in low-and middle-income countries. Obesity is a well-known risk factor for diabetes, and current data project a continuous increase in diabetes prevalence worldwide in obese individuals.

Neuron tracing from light microscopy images: automation, deep learning and bench testing.

Motivation: Large-scale neuronal morphologies are essential to neuronal typing, connectivity characterization and brain modeling. It is widely accepted that automation is critical to the production of neuronal morphology. Despite previous survey papers about neuron tracing from light microscopy data in the last decade, thanks to the rapid development of the field, there is a need to update recent progress in a review focusing on new methods and remarkable applications.

Machine learning classification reveals robust morphometric biomarker of glial and neuronal arbors.

Neurons and glia are the two main cell classes in the nervous systems of most animals. Although functionally distinct, neurons and glia are both characterized by multiple branching arbors stemming from the cell bodies. Glial processes are generally known to form smaller trees than neuronal dendrites.

Critical Requirements for the Initiation of a Cardiac Arrhythmia in Rat Ventricle: How Many Myocytes?

Cardiovascular disease is the leading cause of death worldwide due in a large part to arrhythmia. In order to understand how calcium dynamics play a role in arrhythmogenesis, normal and dysfunctional Ca signaling in a subcellular, cellular, and tissued level is examined using cardiac ventricular myocytes at a high temporal and spatial resolution using multiscale computational modeling. Ca sparks underlie normal excitation-contraction coupling.

Normalized unitary synaptic signaling of the hippocampus and entorhinal cortex predicted by deep learning of experimental recordings.

Biologically realistic computer simulations of neuronal circuits require systematic data-driven modeling of neuron type-specific synaptic activity. However, limited experimental yield, heterogeneous recordings conditions, and ambiguous neuronal identification have so far prevented the consistent characterization of synaptic signals for all connections of any neural system. We introduce a strategy to overcome these challenges and report a comprehensive synaptic quantification among all known neuron types of the hippocampal-entorhinal network.

Quantification of neuron types in the rodent hippocampal formation by data mining and numerical optimization.

Quantifying the population sizes of distinct neuron types in different anatomical regions is an essential step towards establishing a brain cell census. Although estimates exist for the total neuronal populations in different species, the number and definition of each specific neuron type are still intensively investigated. Hippocampome.

A Stochastic Spatiotemporal Model of Rat Ventricular Myocyte Calcium Dynamics Demonstrated Necessary Features for Calcium Wave Propagation.

Calcium (Ca) plays a central role in the excitation and contraction of cardiac myocytes. Experiments have indicated that calcium release is stochastic and regulated locally suggesting the possibility of spatially heterogeneous calcium levels in the cells. This spatial heterogeneity might be important in mediating different signaling pathways.