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 (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, 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, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey.

Microglia are tissue macrophages of the central nervous system that monitor brain homeostasis and react upon neuronal damage and stress. Aging and neurodegeneration induce a hypersensitive, pro-inflammatory phenotype, referred to as primed microglia. To determine the gene expression signature of priming, the transcriptomes of microglia in aging, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) mouse models were compared using Weighted Gene Co-expression Network Analysis (WGCNA).

Aging is regarded as a major risk factor for neurodegenerative diseases. Thus, a better understanding of the similarities between the aging process and neurodegenerative diseases at the cellular and molecular level may reveal better understanding of this detrimental relationship. In the present study, we mined publicly available gene expression datasets from healthy individuals and patients affected by neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and Huntington's disease) across a broad age spectrum and compared those with mouse aging and mouse cell-type specific gene expression profiles. We performed weighted gene co-expression network analysis (WGCNA) and found a gene network strongly related with both aging and neurodegenerative diseases. This network was significantly enriched with a microglial signature as imputed from cell type-specific sequencing data. Since mouse models are extensively used for the study of human diseases, we further compared these human gene regulatory networks with age-specific mouse brain transcriptomes. We discovered significantly preserved networks with both human aging and human disease and identified 17 shared genes in the top-ranked immune/microglia module, among which we found five human hub genes TYROBP, FCER1G, ITGB2, MYO1F, PTPRC, and two mouse hub genes Trem2 and C1qa. Taken together, these results support the hypothesis that microglia are key players involved in human aging and neurodegenerative diseases, and suggest that mouse models should be appropriate for studying these microglial changes in human.

We describe convergent evidence from transcriptomics, morphology, and physiology for a specialized GABAergic neuron subtype in human cortex. Using unbiased single-nucleus RNA sequencing, we identify ten GABAergic interneuron subtypes with combinatorial gene signatures in human cortical layer 1 and characterize a group of human interneurons with anatomical features never described in rodents, having large 'rosehip'-like axonal boutons and compact arborization. These rosehip cells show an immunohistochemical profile (GAD1+CCK+, CNR1-SST-CALB2-PVALB-) matching a single transcriptomically defined cell type whose specific molecular marker signature is not seen in mouse cortex. Rosehip cells in layer 1 make homotypic gap junctions, predominantly target apical dendritic shafts of layer 3 pyramidal neurons, and inhibit backpropagating pyramidal action potentials in microdomains of the dendritic tuft. These cells are therefore positioned for potent local control of distal dendritic computation in cortical pyramidal neurons.

High-throughput sequencing is gradually replacing microarrays as the preferred method for studying mRNA expression levels, providing nucleotide resolution and accurately measuring absolute expression levels of almost any transcript, known or novel. However, existing microarray data from clinical, pharmaceutical, and academic settings represent valuable and often underappreciated resources, and methods for assessing and improving the quality of these data are lacking.

GABAergic interneurons are essential for neural circuit function, and their loss or dysfunction is implicated in human neuropsychiatric disease. In vitro methods for interneuron generation hold promise for studying human cellular and functional properties and, ultimately, for therapeutic cell replacement. Here we describe a protocol for generating cortical interneurons from hESCs and analyze the properties and maturation time course of cell types using single-cell RNA-seq. We find that the cell types produced mimic in vivo temporal patterns of neuron and glial production, with immature progenitors and neurons observed early and mature cortical neurons and glial cell types produced late. By comparing the transcriptomes of immature interneurons to those of more mature neurons, we identified genes important for human interneuron differentiation. Many of these genes were previously implicated in neurodevelopmental and neuropsychiatric disorders.

Specimen data in taxonomic literature are among the highest quality primary biodiversity data. Innovative cybertaxonomic journals are using workflows that maintain data structure and disseminate electronic content to aggregators and other users; such structure is lost in traditional taxonomic publishing. Legacy taxonomic literature is a vast repository of knowledge about biodiversity. Currently, access to that resource is cumbersome, especially for non-specialist data consumers. Markup is a mechanism that makes this content more accessible, and is especially suited to machine analysis. Fine-grained XML (Extensible Markup Language) markup was applied to all (37) open-access articles published in the journal Zootaxa containing treatments on spiders (Order: Araneae). The markup approach was optimized to extract primary specimen data from legacy publications. These data were combined with data from articles containing treatments on spiders published in Biodiversity Data Journal where XML structure is part of the routine publication process. A series of charts was developed to visualize the content of specimen data in XML-tagged taxonomic treatments, either singly or in aggregate. The data can be filtered by several fields (including journal, taxon, institutional collection, collecting country, collector, author, article and treatment) to query particular aspects of the data. We demonstrate here that XML markup using GoldenGATE can address the challenge presented by unstructured legacy data, can extract structured primary biodiversity data which can be aggregated with and jointly queried with data from other Darwin Core-compatible sources, and show how visualization of these data can communicate key information contained in biodiversity literature. We complement recent studies on aspects of biodiversity knowledge using XML structured data to explore 1) the time lag between species discovry and description, and 2) the prevelence of rarity in species descriptions.

The Human Reference Atlas (HRA) aims to map all of the cells of the human body to advance biomedical research and clinical practice. This Perspective presents collaborative work by members of 16 international consortia on two essential and interlinked parts of the HRA: (1) three-dimensional representations of anatomy that are linked to (2) tables that name and interlink major anatomical structures, cell types, plus biomarkers (ASCT+B). We discuss four examples that demonstrate the practical utility of the HRA.

The advancement of single-cell RNA-sequencing technologies has led to an explosion of cell type definitions across multiple organs and organisms. While standards for data and metadata intake are arising, organization of cell types has largely been left to individual investigators, resulting in widely varying nomenclature and limited alignment between taxonomies. To facilitate cross-dataset comparison, the Allen Institute created the common cell type nomenclature (CCN) for matching and tracking cell types across studies that is qualitatively similar to gene transcript management across different genome builds. The CCN can be readily applied to new or established taxonomies and was applied herein to diverse cell type datasets derived from multiple quantifiable modalities. The CCN facilitates assigning accurate yet flexible cell type names in the mammalian cortex as a step toward community-wide efforts to organize multi-source, data-driven information related to cell type taxonomies from any organism.

Genes associated with risk for brain disease exhibit characteristic expression patterns that reflect both anatomical and cell type relationships. Brain-wide transcriptomic patterns of disease risk genes provide a molecular-based signature, based on differential co-expression, that is often unique to that disease. Brain diseases can be compared and aggregated based on the similarity of their signatures which often associates diseases from diverse phenotypic classes. Analysis of 40 common human brain diseases identifies 5 major transcriptional patterns, representing tumor-related, neurodegenerative, psychiatric and substance abuse, and 2 mixed groups of diseases affecting basal ganglia and hypothalamus. Further, for diseases with enriched expression in cortex, single-nucleus data in the middle temporal gyrus (MTG) exhibits a cell type expression gradient separating neurodegenerative, psychiatric, and substance abuse diseases, with unique excitatory cell type expression differentiating psychiatric diseases. Through mapping of homologous cell types between mouse and human, most disease risk genes are found to act in common cell types, while having species-specific expression in those types and preserving similar phenotypic classification within species. These results describe structural and cellular transcriptomic relationships of disease risk genes in the adult brain and provide a molecular-based strategy for classifying and comparing diseases, potentially identifying novel disease relationships.

Developmental changes in the temporal and spatial regulation of gene expression drive the emergence of normal mature brain function, while disruptions in these processes underlie many neurodevelopmental abnormalities. To solidify our foundational knowledge of such changes in a primate brain with an extended period of postnatal maturation like in human, we investigated the whole-genome transcriptional profiles of rhesus monkey brains from birth to adulthood. We found that gene expression dynamics are largest from birth through infancy, after which gene expression profiles transition to a relatively stable state by young adulthood. Biological pathway enrichment analysis revealed that genes more highly expressed at birth are associated with cell adhesion and neuron differentiation, while genes more highly expressed in juveniles and adults are associated with cell death. Neocortex showed significantly greater differential expression over time than subcortical structures, and this trend likely reflects the protracted postnatal development of the cortex. Using network analysis, we identified 27 co-expression modules containing genes with highly correlated expression patterns that are associated with specific brain regions, ages or both. In particular, one module with high expression in neonatal cortex and striatum that decreases during infancy and juvenile development was significantly enriched for autism spectrum disorder (ASD)-related genes. This network was enriched for genes associated with axon guidance and interneuron differentiation, consistent with a disruption in the formation of functional cortical circuitry in ASD.

No abstract available

The family Eresidae C. L. Koch, 1850 is reviewed at the genus level. The family comprises nine genera including one new genus. They are: Adonea Simon, 1873, Dorceus C. L. Koch, 1846, Dresserus Simon, 1876, Eresus Walckenaer, 1805, Gandanameno Lehtinen, 1967, Loureediagen. n., ParadoneaLawrence, 1968, Seothyra Purcell, 1903, and Stegodyphus Simon, 1873. A key to all genera and major lineages is provided along with corresponding diagnoses, as well as descriptions of selected species. These are documented with collections of photographs, scanning electron micrographs, and illustrations. A new phylogeny of Eresidae based on molecular sequence data expands on a previously published analysis. A species of the genus Paradonea Lawrence, 1968 is sequenced and placed phylogenetically for the first time. New sequences from twenty Gandanameno Lehtinen, 1967 specimens were added to investigate species limits within the genus. The genus Loureediagen. n. is proposed to accommodate Eresus annulipes Lucas, 1857. Two species, Eresus semicanus Simon, 1908 and Eresus jerbae El-Hennawy, 2005, are synonymized with Loureedia annulipescomb. n. One new species, Paradonea presleyisp. n. is described. Eresus algericus El-Hennawy, 2004 is transferred to Adonea Simon, 1873. The female of Dorceus fastuosus C. L. Koch, 1846 is described for the first time. The first figures depicting Paradonea splendens (Lawrence, 1936) are presented.

The study of parasitoids and their hosts suffers from a lack of reliable taxonomic data. We use a combination of morphological characters and DNA sequences to produce taxonomic determinations that can be verified with reference to specimens in an accessible collection and DNA barcode sequences posted to the Barcode of Life database (BOLD). We demonstrate that DNA can be successfully extracted from consumed host spiders and the shed pupal case of a wasp using non-destructive methods. We found Acrodactylaquadrisculpta to be a parasitoid of Tetragnathamontana; Zatypotapercontatoria and Zatypotabohemani both are parasitoids of Neottiurabimaculata. Zatypotaanomala is a parasitoid of an as yet unidentified host in the family Dictynidae, but the host species may be possible to identify in the future as the library of reference sequences on BOLD continues to grow. The study of parasitoids and their hosts traditionally requires specialized knowledge and techniques, and accumulating data is a slow process. DNA barcoding could allow more professional and amateur naturalists to contribute data to this field of study. A publication venue dedicated to aggregating datasets of all sizes online is well suited to this model of distributed science.

The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure and function. We applied a correlation-based metric called differential stability to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing mesoscale genetic organization. The genes with the highest differential stability are highly biologically relevant, with enrichment for brain-related annotations, disease associations, drug targets and literature citations. Using genes with high differential stability, we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely patterned genes displayed marked shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry.

Introduction: Patients with glioblastoma (GBM), one of the most aggressive forms of primary brain tumors, exhibit a wide range of neurologic signs, ranging from headaches to neurologic deficits and cognitive impairment, at first clinical presentation. While such variability is attributed to inter-individual differences in increased intracranial pressure, tumor infiltration, and vascular compromise, a direct association with disease stage, tumor size and location, edema, and necrotic cell death has yet to be established. The lack of specificity of neurologic symptoms often confounds the diagnosis of GBM. It also limits clinicians' ability to elect treatment regimens that not only prolong survival but also promote symptom management and high quality of life. Methods: To decipher the heterogeneous presentation of neurologic symptoms in GBM, we investigated differences in the molecular makeup of tumors from patients with and without preoperative neurologic deficits. We used the Ivy GAP (Ivy Glioblastoma Atlas Project) database to integrate RNA sequencing data from histologically defined GBM tumor compartments and neurologic examination records for 41 patients. We investigated the association of neurologic deficits with various tumor and patient attributes. We then performed differential gene expression and co-expression network analysis to identify a transcriptional signature specific to neurologic deficits in GBM. Using functional enrichment analysis, we finally provided a comprehensive and detailed characterization of involved pathways and gene interactions. Results: An exploratory investigation of the association of tumor and patient variables with the early development of neurologic deficits in GBM revealed a lack of robust and consistent clinicopathologic prognostic factors. We detected significant differences in the expression of 728 genes (FDR-adjusted p-value ≤ 0.05 and relative fold-change ≥ 1.5), unique to the cellular tumor (CT) anatomical compartment, between neurologic deficit groups. Upregulated differentially expressed genes in CT were enriched for mesenchymal subtype-predictive genes. Applying a systems approach, we then identified co-expressed gene sets that correlated with neurological deficit manifestation (FDR-adjusted p-value < 0.1). Collectively, these findings uncovered significantly enriched immune activation, oxidative stress response, and cytokine-mediated proinflammatory processes. Conclusion: Our study posits that inflammatory processes, as well as a mesenchymal tumor subtype, are implicated in the pathophysiology of preoperative neurologic deficits in GBM.

Transcriptomic profiling of complex tissues by single-nucleus RNA-sequencing (snRNA-seq) affords some advantages over single-cell RNA-sequencing (scRNA-seq). snRNA-seq provides less biased cellular coverage, does not appear to suffer cell isolation-based transcriptional artifacts, and can be applied to archived frozen specimens. We used well-matched snRNA-seq and scRNA-seq datasets from mouse visual cortex to compare cell type detection. Although more transcripts are detected in individual whole cells (~11,000 genes) than nuclei (~7,000 genes), we demonstrate that closely related neuronal cell types can be similarly discriminated with both methods if intronic sequences are included in snRNA-seq analysis. We estimate that the nuclear proportion of total cellular mRNA varies from 20% to over 50% for large and small pyramidal neurons, respectively. Together, these results illustrate the high information content of nuclear RNA for characterization of cellular diversity in brain tissues.

As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer's disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology and cognitive abilities with advancing age, indicative of individual variation in resilience to pathology. Here, we generated a comprehensive neuropathological, molecular, and transcriptomic characterization of hippocampus and two regions cortex in 107 aged donors (median = 90) from the Adult Changes in Thought (ACT) study as a freely-available resource (http://aging.brain-map.org/). We confirm established associations between AD pathology and dementia, albeit with increased, presumably aging-related variability, and identify sets of co-expressed genes correlated with pathological tau and inflammation markers. Finally, we demonstrate a relationship between dementia and RNA quality, and find common gene signatures, highlighting the importance of properly controlling for RNA quality when studying dementia.

The family Symphytognathidae is reported from Thailand for the first time. Three new species: Anapistula choojaiae sp. nov., Crassignatha seeliam sp. nov., and Crassignatha seedam sp. nov. are described and illustrated. Distribution is expanded and additional morphological data are reported for Patu shiluensis Lin & Li, 2009. Specimens were collected in Thailand between July and August 2018. The newly described species were found in the north mountainous region of Chiang Mai, and Patu shiluensis was collected in the coastal region of Phuket. DNA sequences are provided for all the species here studied. The relations of these symphytognathid species were tested using previously published phylogenetic analyses on micro orb-weavers. Also, we used micro CT analysis to build 3D models of the male genitalia and somatic characters of two species of Crassignatha Wunderlich, 1995. The molecular phylogeny and 3D models were used to discuss the taxonomy and circumscription of the currently valid symphytognathid genera, with focus on Crassignatha and Patu Marples, 1951. Based on this, three new combinations are suggested: Crassignatha bicorniventris (Lin & Li, 2009), comb. nov., Crassignatha quadriventris (Lin & Li, 2009), comb. nov., and Crassignatha spinathoraxi (Lin & Li, 2009), comb. nov. A new record of Crassignatha danaugirangensisMiller et al. 2014 is reported from Brunei.

The late neuropathological effects of traumatic brain injury have yet to be fully elucidated, particularly with respect to community-based cohorts. To contribute to this critical gap in knowledge, we designed a multimodal neuropathological study, integrating traditional and quantitative approaches to detect pathologic changes in 532 consecutive brain autopsies from participants in the Adult Changes in Thought (ACT) study. Diagnostic evaluation including assessment for chronic traumatic encephalopathy (CTE) and quantitative immunoassay-based methods were deployed to examine levels of pathological (hyperphosphorylated) tau (pTau) and amyloid (A) β in brains from ACT participants with (n = 107) and without (n = 425) history of remote TBI with loss of consciousness (w/LOC). Further neuropathological assessments included immunohistochemistry for α-synuclein and phospho-TDP-43 pathology and astro- (GFAP) and micro- (Iba1) gliosis, mass spectrometry analysis of free radical injury, and gene expression evaluation (RNA sequencing) in a smaller sub-cohort of matched samples (49 cases with TBI and 49 non-exposed matched controls). Out of 532 cases, only 3 (0.6%-none with TBI w/LOC history) showed evidence of the neuropathologic signature of chronic traumatic encephalopathy (CTE). Across the entire cohort, the levels of pTau and Aβ showed expected differences for brain region (higher levels in temporal cortex), neuropathological diagnosis (higher in participants with Alzheimer's disease), and APOE genotype (higher in participants with one or more APOE ε4 allele). However, no differences in PHF-tau or Aβ1-42 were identified by Histelide with respect to the history of TBI w/LOC. In a subset of TBI cases with more carefully matched control samples and more extensive analysis, those with TBI w/LOC history had higher levels of hippocampal pTau but no significant differences in Aβ, α-synuclein, pTDP-43, GFAP, Iba1, or free radical injury. RNA-sequencing also did not reveal significant gene expression associated with any measure of TBI exposure. Combined, these findings suggest long term neuropathological changes associated with TBI w/LOC may be subtle, involve non-traditional pathways of neurotoxicity and neurodegeneration, and/or differ from those in autopsy cohorts specifically selected for neurotrauma exposure.