Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography— the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.

SummaryThe anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high resolution transcriptional atlas of rhesus monkey brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical parcellation of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons, and cortical layers and areas acquire adult-like molecular profiles surprisingly late postnatally. Disparate cell populations exhibit distinct developmental timing but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, and approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny.

Spreading depolarizations (SDs) are recognized as actors in neurological disorders as diverse as migraine and traumatic brain injury (TBI). Migraine aura involves sensory percepts, suggesting that sensory cortices might be intrinsically susceptible to SDs. We used optical imaging, MRI, and field potential and potassium electrode recordings in mice and electrocorticographic recordings in humans to determine the susceptibility of different brain regions to SDs. Optical imaging experiments in mice under isoflurane anesthesia showed that both cortical spreading depression and terminal anoxic depolarization arose preferentially in the whisker barrel region of parietal sensory cortex. MRI recordings under isoflurane, ketamine/xylazine, ketamine/isoflurane, and urethane anesthesia demonstrated that the depolarizations did not propagate from a subcortical source. Potassium concentrations showed larger increases in sensory cortex, suggesting a mechanism of susceptibility. Sensory stimulation biased the timing but not the location of depolarization onset. In humans with TBI, there was a trend toward increased incidence of SDs in parietal/temporal sensory cortex compared with other regions. In conclusion, SDs are inducible preferentially in primary sensory cortex in mice and most likely in humans. This tropism can explain the predominant sensory phenomenology of migraine aura. It also demonstrates that sensory cortices are vulnerable in brain injury.

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An estimated 5 million Americans have congestive heart failure (CHF) and one in five over the age of 40 will develop CHF. There are numerous examples of CHF patients living beyond the years normally expected for people with the disease, usually attributed to taking an active role in disease management. A relatively new alternative for CHF outpatient care is telemedicine and e-health. We investigated the effects of a 6-week in-home telemedicine education and monitoring program for those with systolic dysfunction on the utilization of health care resources. We also measured the effects of the unit 4.5 months after its removal (a total of 6 months post introduction of the unit into the home). Concurrently, we assessed participants' perceptions of the value of having a telemedicine unit. Participants in the telemedicine group reported weighing more times a week with less variability than did the control group. Telemedicine led to a reduction in physician and emergency department visits and those in the experimental group reported the unit facilitating self-care, though this was not significantly different from the control group (possibly due to small sample size). These findings suggest a possibility for improvement in control of CHF when telemedicine is implemented. Our review of the literature also supports the role of telemedicine in facilitating home health care and self-management for CHF patients. There are many challenges still to be addressed before this potential can be reached and further research is needed to identify opportunities in telemedicine.

Laboratory experiments were developed to introduce students to the quantitation of drugs of abuse by high performance liquid chromatography-tandem mass spectrometry (LC−MS/MS). Undergraduate students were introduced to internal standard quantitation and the LC−MS/MS method optimization for cocaine. Cocaine extracted from paper currency was analyzed with a simple and rapid LC−MS/MS method. Students in advanced laboratories determined the amount of amphetamine, methamphetamine, and oxycodone on currency in addition to cocaine. The LC−MS/MS method has a short run time (2.5 min) to allow for a high throughput of student samples.

By using Rh–H catalysis, we couple α‐nitroesters and alkynes to prepare α‐amino‐acid precursors. This atom‐economical strategy generates two contiguous stereocenters, with high enantio‐ and diastereocontrol. In this transformation, the alkyne undergoes isomerization to generate a RhIII–π‐allyl electrophile, which is trapped by an α‐nitroester nucleophile. A subsequent reduction with In powder transforms the allylic α‐nitroesters to the corresponding α,α‐disubstituted α‐amino esters.