Connectome-driven neural inventory of a complete visual system.

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brain's volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing.

NeuronBridge: an intuitive web application for neuronal morphology search across large data sets.

Background: Neuroscience research in Drosophila is benefiting from large-scale connectomics efforts using electron microscopy (EM) to reveal all the neurons in a brain and their connections. To exploit this knowledge base, researchers relate a connectome's structure to neuronal function, often by studying individual neuron cell types. Vast libraries of fly driver lines expressing fluorescent reporter genes in sets of neurons have been created and imaged using confocal light microscopy (LM), enabling the targeting of neurons for experimentation.

The cell-type-specific spatial organization of the anterior thalamic nuclei of the mouse brain.

Understanding the cell-type composition and spatial organization of brain regions is crucial for interpreting brain computation and function. In the thalamus, the anterior thalamic nuclei (ATN) are involved in a wide variety of functions, yet the cell-type composition of the ATN remains unmapped at a single-cell and spatial resolution. Combining single-cell RNA sequencing, spatial transcriptomics, and multiplexed fluorescent in situ hybridization, we identify three discrete excitatory cell-type clusters that correspond to the known nuclei of the ATN and uncover marker genes, molecular pathways, and putative functions of these cell types.

Sharp cell-type-identity changes differentiate the retrosplenial cortex from the neocortex.

The laminae of the neocortex are fundamental processing layers of the mammalian brain. Notably, such laminae are believed to be relatively stereotyped across short spatial scales such that shared laminae between nearby brain regions exhibit similar constituent cells. Here, we consider a potential exception to this rule by studying the retrosplenial cortex (RSC), a brain region known for sharp cytoarchitectonic differences across its granular-dysgranular border.

A searchable image resource of GAL4 driver expression patterns with single neuron resolution.

Precise, repeatable genetic access to specific neurons via GAL4/UAS and related methods is a key advantage of neuroscience. Neuronal targeting is typically documented using light microscopy of full GAL4 expression patterns, which generally lack the single-cell resolution required for reliable cell type identification. Here, we use stochastic GAL4 labeling with the MultiColor FlpOut approach to generate cellular resolution confocal images at large scale.

Neuronal cell types, projections, and spatial organization of the central amygdala.

The central amygdala (CEA) has been richly studied for interpreting function and behavior according to specific cell types and circuits. Such work has typically defined molecular cell types by classical inhibitory marker genes; consequently, whether marker-gene-defined cell types exhaustively cover the CEA and co-vary with connectivity remains unresolved. Here, we combined single-cell RNA sequencing, multiplexed fluorescent hybridization, immunohistochemistry, and long-range projection mapping to derive a "bottom-up" understanding of CEA cell types.

Print: An open access tool for EM connectomics.

Due to advances in electron microscopy and deep learning, it is now practical to reconstruct a connectome, a description of neurons and the chemical synapses between them, for significant volumes of neural tissue. Smaller past reconstructions were primarily used by domain experts, could be handled by downloading data, and performance was not a serious problem. But new and much larger reconstructions upend these assumptions.

Whole-cell organelle segmentation in volume electron microscopy.

Cells contain hundreds of organelles and macromolecular assemblies. Obtaining a complete understanding of their intricate organization requires the nanometre-level, three-dimensional reconstruction of whole cells, which is only feasible with robust and scalable automatic methods. Here, to support the development of such methods, we annotated up to 35 different cellular organelle classes-ranging from endoplasmic reticulum to microtubules to ribosomes-in diverse sample volumes from multiple cell types imaged at a near-isotropic resolution of 4 nm per voxel with focused ion beam scanning electron microscopy (FIB-SEM).

Spatially patterned excitatory neuron subtypes and projections of the claustrum.

The claustrum is a functionally and structurally complex brain region, whose very spatial extent remains debated. Histochemical-based approaches typically treat the claustrum as a relatively narrow anatomical region that primarily projects to the neocortex, whereas circuit-based approaches can suggest a broader claustrum region containing projections to the neocortex and other regions. Here, in the mouse, we took a bottom-up and cell-type-specific approach to complement and possibly unite these seemingly disparate conclusions.

Multidisciplinary prosthetic rehabilitation of an adult patient with cleidocranial dysplasia by using a rapid external distraction device: A clinical report.

The multidisciplinary treatment of a 41-year-old man with cleidocranial dysplasia is described. A rapid external distraction device was used to reposition the maxilla before the prosthodontic rehabilitation.

A connectome and analysis of the adult central brain.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly . Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets.

Extensive and spatially variable within-cell-type heterogeneity across the basolateral amygdala.

The basolateral amygdala complex (BLA), extensively connected with both local amygdalar nuclei as well as long-range circuits, is involved in a diverse array of functional roles. Understanding the mechanisms of such functional diversity will be greatly informed by understanding the cell-type-specific landscape of the BLA. Here, beginning with single-cell RNA sequencing, we identified both discrete and graded continuous gene-expression differences within the mouse BLA.

Estimating the power of sequence covariation for detecting conserved RNA structure.

Unlabelled: Pairwise sequence covariations are a signal of conserved RNA secondary structure. We describe a method for distinguishing when lack of covariation signal can be taken as evidence against a conserved RNA structure, as opposed to when a sequence alignment merely has insufficient variation to detect covariations. We find that alignments for several long non-coding RNAs previously shown to lack covariation support do have adequate covariation detection power, providing additional evidence against their proposed conserved structures.

The subiculum is a patchwork of discrete subregions.

In the hippocampus, the classical pyramidal cell type of the subiculum acts as a primary output, conveying hippocampal signals to a diverse suite of downstream regions. Accumulating evidence suggests that the subiculum pyramidal cell population may actually be comprised of discrete subclasses. Here, we investigated the extent and organizational principles governing pyramidal cell heterogeneity throughout the mouse subiculum.

Do denture processing techniques affect the mechanical properties of denture teeth?

Statement Of Problem: Denture tooth fracture may limit the longevity of dental prostheses. Whether the strength of the denture tooth material is affected by the denture processing technique is unclear.

Purpose: The purpose of this in vitro study was to investigate whether the denture processing technique affects the mechanical properties of denture tooth materials.

A statistical test for conserved RNA structure shows lack of evidence for structure in lncRNAs.

Many functional RNAs have an evolutionarily conserved secondary structure. Conservation of RNA base pairing induces pairwise covariations in sequence alignments. We developed a computational method, R-scape (RNA Structural Covariation Above Phylogenetic Expectation), that quantitatively tests whether covariation analysis supports the presence of a conserved RNA secondary structure.

The Dfam database of repetitive DNA families.

Repetitive DNA, especially that due to transposable elements (TEs), makes up a large fraction of many genomes. Dfam is an open access database of families of repetitive DNA elements, in which each family is represented by a multiple sequence alignment and a profile hidden Markov model (HMM). The initial release of Dfam, featured in the 2013 NAR Database Issue, contained 1143 families of repetitive elements found in humans, and was used to produce more than 100 Mb of additional annotation of TE-derived regions in the human genome, with improved speed.

HMMER web server: 2015 update.

The HMMER website, available at http://www.ebi.ac.

Skylign: a tool for creating informative, interactive logos representing sequence alignments and profile hidden Markov models.

Background: Logos are commonly used in molecular biology to provide a compact graphical representation of the conservation pattern of a set of sequences. They render the information contained in sequence alignments or profile hidden Markov models by drawing a stack of letters for each position, where the height of the stack corresponds to the conservation at that position, and the height of each letter within a stack depends on the frequency of that letter at that position.

Results: We present a new tool and web server, called Skylign, which provides a unified framework for creating logos for both sequence alignments and profile hidden Markov models.

iPfam: a database of protein family and domain interactions found in the Protein Data Bank.

The database iPfam, available at http://ipfam.org, catalogues Pfam domain interactions based on known 3D structures that are found in the Protein Data Bank, providing interaction data at the molecular level. Previously, the iPfam domain-domain interaction data was integrated within the Pfam database and website, but it has now been migrated to a separate database.

Pfam: the protein families database.

Pfam, available via servers in the UK (http://pfam.sanger.ac.

Dfam: a database of repetitive DNA based on profile hidden Markov models.

We present a database of repetitive DNA elements, called Dfam (http://dfam.janelia.org).

The Pfam protein families database.

Pfam is a widely used database of protein families, currently containing more than 13,000 manually curated protein families as of release 26.0. Pfam is available via servers in the UK (http://pfam.

HMMER web server: interactive sequence similarity searching.

HMMER is a software suite for protein sequence similarity searches using probabilistic methods. Previously, HMMER has mainly been available only as a computationally intensive UNIX command-line tool, restricting its use. Recent advances in the software, HMMER3, have resulted in a 100-fold speed gain relative to previous versions.

Patterns of somatic mutation in human cancer genomes.

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers.