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The genetic mechanisms regulating the brain and behaviour across the lifespan are poorly understood. We found that lifespan transcriptome trajectories describe a calendar of gene regulatory events in the brain of humans and mice. Transcriptome trajectories defined a sequence of gene expression changes in neuronal, glial and endothelial cell-types, which enabled prediction of age from tissue samples. A major lifespan landmark was the peak change in trajectories occurring in humans at 26 years and in mice at 5 months of age. This species-conserved peak was delayed in females and marked a reorganization of expression of synaptic and schizophrenia-susceptibility genes. The lifespan calendar predicted the characteristic age of onset in young adults and sex differences in schizophrenia. We propose a genomic program generates a lifespan calendar of gene regulation that times age-dependent molecular organization of the brain and mutations that interrupt the program in young adults cause schizophrenia.

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Surface reconstruction methods allow advanced analysis of structural and functional brain data beyond what can be achieved using volumetric images alone. Automated generation of cortical surface meshes from 3D brain MRI often leads to topological defects and geometrical artifacts that must be corrected to permit subsequent analysis. Here, we propose a novel method to repair topological defects using a surface reconstruction that relies on spherical harmonics. First, during reparameterization of the surface using a tiled platonic solid, the original MRI intensity values are used as a basis to select either a "fill" or "cut" operation for each topological defect. We modify the spherical map of the uncorrected brain surface mesh, such that certain triangles are favored while searching for the bounding triangle during reparameterization. Then, a low-pass filtered alternative reconstruction based on spherical harmonics is patched into the reconstructed surface in areas that previously contained defects. Self-intersections are repaired using a local smoothing algorithm that limits the number of affected points to less than 0.1% of the total, and as a last step, all modified points are adjusted based on the T1 intensity. We found that the corrected reconstructions have reduced distance error metrics compared with a "gold standard" surface created by averaging 12 scans of the same brain. Ninety-three percent of the topological defects in a set of 10 scans of control subjects were accurately corrected. The entire process takes 6-8 min of computation time. Further improvements are discussed, especially regarding the use of the T1-weighted image to make corrections.

A review of photodetectors for optical detection in biological applications is presented. The intent is to provide an overview of the performance metrics and trade-offs among popular photodetectors in order to facilitate an easier match among the photodetector, biological stimulus, and optical pathway. The characteristics and nonidealities of fluorescent and phosphorescent reporters, and the properties of optical components such as filters, lenses, and light sources, are reviewed. By accounting for sources of noise in these components, it is shown how to determine metrics for the optical system that can then be converted to photodetector metrics. Defined photodetector metrics include the quantum efficiency, responsivity, noise-equivalent power, detectivity, gain, dark current, response time, and noise spectrum. The operating principles and performance trade-offs of photodetectors are reviewed, and emphasis is placed on photodetectors for integrated compact systems. Top commercial candidates for photodetectors for detecting light emitted from reporters are the photomultiplier tube, avalanche photodiode, and charge-coupled device. Focus is placed on new developments in complementary metal-oxide-semiconductor structures that can provide low-cost, low-power, and low-voltage alternatives to traditional approaches to biological imaging. Reviewed device structures are presented in the context of supporting the development of laboratory-based instruments and compact fully-integrated systems.