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.

Petascale pipeline for precise alignment of images from serial section electron microscopy.

The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy is often limited by the preceding step of aligning 2D section images to create a 3D image stack. Precise and robust alignment in the presence of image artifacts is challenging, especially as datasets are attaining the petascale.

Architecture and dynamics of a desmosome-endoplasmic reticulum complex.

The endoplasmic reticulum (ER) forms a dynamic network that contacts other cellular membranes to regulate stress responses, calcium signalling and lipid transfer. Here, using high-resolution volume electron microscopy, we find that the ER forms a previously unknown association with keratin intermediate filaments and desmosomal cell-cell junctions. Peripheral ER assembles into mirror image-like arrangements at desmosomes and exhibits nanometre proximity to keratin filaments and the desmosome cytoplasmic plaque.

A scalable and modular automated pipeline for stitching of large electron microscopy datasets.

Serial-section electron microscopy (ssEM) is the method of choice for studying macroscopic biological samples at extremely high resolution in three dimensions. In the nervous system, nanometer-scale images are necessary to reconstruct dense neural wiring diagrams in the brain, so -called . The data that can comprise of up to 10 individual EM images must be assembled into a volume, requiring seamless 2D registration from physical section followed by 3D alignment of the stitched sections.

Precision screening for familial hypercholesterolaemia: a machine learning study applied to electronic health encounter data.

Background: Cardiovascular outcomes for people with familial hypercholesterolaemia can be improved with diagnosis and medical management. However, 90% of individuals with familial hypercholesterolaemia remain undiagnosed in the USA. We aimed to accelerate early diagnosis and timely intervention for more than 1·3 million undiagnosed individuals with familial hypercholesterolaemia at high risk for early heart attacks and strokes by applying machine learning to large health-care encounter datasets.

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.

Luciferin production and luciferase transcription in the bioluminescent copepod .

Bioluminescent copepods are often the most abundant marine zooplankton and play critical roles in oceanic food webs. copepods exhibit particularly bright bioluminescence, and the molecular basis of their light production has just recently begun to be explored. Here we add to this body of work by transcriptomically profiling , a common species found in temperate, northern, and southern latitudes.

A Complete Electron Microscopy Volume of the Brain of Adult Drosophila melanogaster.

Drosophila melanogaster has a rich repertoire of innate and learned behaviors. Its 100,000-neuron brain is a large but tractable target for comprehensive neural circuit mapping. Only electron microscopy (EM) enables complete, unbiased mapping of synaptic connectivity; however, the fly brain is too large for conventional EM.

Domain-Targeted Metabolomics Delineates the Heterocycle Assembly Steps of Colibactin Biosynthesis.

Modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) comprise giant multidomain enzymes responsible for the "assembly line" biosynthesis of many genetically encoded small molecules. Site-directed mutagenesis, protein biochemical, and structural studies have focused on elucidating the catalytic mechanisms of individual multidomain proteins and protein domains within these megasynthases. However, probing their functions at the cellular level typically has invoked the complete deletion (or overexpression) of multidomain-encoding genes or combinations of genes and comparing those mutants with a control pathway.

Metabolite exchange between microbiome members produces compounds that influence behavior.

Animals host multi-species microbial communities (microbiomes) whose properties may result from inter-species interactions; however, current understanding of host-microbiome interactions derives mostly from studies in which elucidation of microbe-microbe interactions is difficult. In exploring how acquires its microbiome, we found that a microbial community influences olfactory and egg-laying behaviors differently than individual members. prefers a - co-culture to the same microorganisms grown individually and then mixed, a response mainly due to the conserved olfactory receptor, metabolism of derived ethanol was necessary, and acetate and its metabolic derivatives were sufficient, for co-culture preference.

Linking Biosynthetic Gene Clusters to their Metabolites via Pathway- Targeted Molecular Networking.

The connection of microbial biosynthetic gene clusters to the small molecule metabolites they encode is central to the discovery and characterization of new metabolic pathways with ecological and pharmacological potential. With increasing microbial genome sequence information being deposited into publicly available databases, it is clear that microbes have the coding capacity for many more biologically active small molecules than previously realized. Of increasing interest are the small molecules encoded by the human microbiome, as these metabolites likely mediate a variety of currently uncharacterized human-microbe interactions that influence health and disease.

Dynamical feature extraction at the sensory periphery guides chemotaxis.

Behavioral strategies employed for chemotaxis have been described across phyla, but the sensorimotor basis of this phenomenon has seldom been studied in naturalistic contexts. Here, we examine how signals experienced during free olfactory behaviors are processed by first-order olfactory sensory neurons (OSNs) of the Drosophila larva. We find that OSNs can act as differentiators that transiently normalize stimulus intensity-a property potentially derived from a combination of integral feedback and feed-forward regulation of olfactory transduction.

Comparative metabolomics and structural characterizations illuminate colibactin pathway-dependent small molecules.

The gene cluster responsible for synthesis of the unknown molecule "colibactin" has been identified in mutualistic and pathogenic Escherichia coli. The pathway endows its producer with a long-term persistence phenotype in the human bowel, a probiotic activity used in the treatment of ulcerative colitis, and a carcinogenic activity under host inflammatory conditions. To date, functional small molecules from this pathway have not been reported.

A red-shifted, fast-relaxing azobenzene photoswitch for visible light control of an ionotropic glutamate receptor.

The use of azobenzene photoswitches has become a dependable method for rapid and exact modulation of biological processes and material science systems. The requirement of ultraviolet light for azobenzene isomerization is not ideal for biological systems due to poor tissue penetration and potentially damaging effects. While modified azobenzene cores with a red-shifted cis-to-trans isomerization have been previously described, they have not yet been incorporated into a powerful method to control protein function: the photoswitchable tethered ligand (PTL) approach.

A GAL4-driver line resource for Drosophila neurobiology.

We established a collection of 7,000 transgenic lines of Drosophila melanogaster. Expression of GAL4 in each line is controlled by a different, defined fragment of genomic DNA that serves as a transcriptional enhancer. We used confocal microscopy of dissected nervous systems to determine the expression patterns driven by each fragment in the adult brain and ventral nerve cord.

High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.

Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms.

Preferred viewing distances for handheld and structurally fixed displays.

This research was conducted to define viewing distance characteristics of individuals engaged in ordinary reading tasks. Specific attention was directed to assessing the potential relationship between observed distance and individual resting point accommodation. Consistent, statistically significant differences were observed across variable handheld and structurally-fixed hardcopy display configuration conditions.

Synthetic smoke with acrolein but not HCl produces pulmonary edema.

The chemical toxins in smoke and not the heat are responsible for the pulmonary edema of smoke inhalation. We developed a synthetic smoke composed of carbon particles (mean diameter of 4.3 microns) to which toxins known to be in smoke, such as HCl or acrolein, could be added one at a time.

Time dependence of the oxygen cost of force development during systole in the canine left ventricle.

To determine whether the oxygen cost of force development in the canine left ventricle is constant throughout systole, we inserted fluid-filled Latex balloons into eight isolated canine left ventricles perfused via support dogs. Balloon volumes were varied by a hydraulic servoactuator designed to withdraw preset volumes rapidly (0.5 ml/msec) beginning at a specified ejection pressure.

Tracer measurements of non-equilibrium volumes of distribution.

According to conventional theory the product of the transport flowrate and the mean transit time of a tracer through a system yields the equilibrium volume of distribution for the tracer, regardless of tracer kinetics or space geometry. Experimental results do not support this notion. The influence of measurement time on the volume measured with a bolus technique is addressed using systems theory to analyze a tissue-impedance form of the Sangren-Sheppard model.