Circuitry mapping of metazoan neural systems is difficult because canonical neural regions (regions containing one or more copies of all components) are large, regional borders are uncertain, neuronal diversity is high, and potential network topologies so numerous that only anatomical ground truth can resolve them. Complete mapping of a specific network requires synaptic resolution, canonical region coverage, and robust neuronal classification. Though transmission electron microscopy (TEM) remains the optimal tool for network mapping, the process of building large serial section TEM (ssTEM) image volumes is rendered difficult by the need to precisely mosaic distorted image tiles and register distorted mosaics. Moreover, most molecular neuronal class markers are poorly compatible with optimal TEM imaging. Our objective was to build a complete framework for ultrastructural circuitry mapping. This framework combines strong TEM-compliant small molecule profiling with automated image tile mosaicking, automated slice-to-slice image registration, and gigabyte-scale image browsing for volume annotation. Specifically we show how ultrathin molecular profiling datasets and their resultant classification maps can be embedded into ssTEM datasets and how scripted acquisition tools (SerialEM), mosaicking and registration (ir-tools), and large slice viewers (MosaicBuilder, Viking) can be used to manage terabyte-scale volumes. These methods enable large-scale connectivity analyses of new and legacy data. In well-posed tasks (e.g., complete network mapping in retina), terabyte-scale image volumes that previously would require decades of assembly can now be completed in months. Perhaps more importantly, the fusion of molecular profiling, image acquisition by SerialEM, ir-tools volume assembly, and data viewers/annotators also allow ssTEM to be used as a prospective tool for discovery in nonneural systems and a practical screening methodology for neurogenetics. Finally, this framework provides a mechanism for parallelization of ssTEM imaging, volume assembly, and data analysis across an international user base, enhancing the productivity of a large cohort of electron microscopists.

Insights into risk factors for olfactory decline are needed, because knowledge about its origin is limited. This impairment has important implications for human health. Several epidemiologic studies of olfaction provide insight into the prevalence of olfactory disorders. Here, we review the major population studies carried out on this topic to date. Our purpose is to characterize knowledge about olfactory disorders from human studies. We also describe the existing methods for measuring the sense of smell in population studies, present recent insights into the epidemiology of smell disorders, and discuss the risk factors identified to date. Synthesis of these data shows that olfactory dysfunction increases as people age and is worse in men. Further study of olfaction is warranted for gaining better information on the etiologies affecting its impairment, research that will have a large public health impact.

The threshold hypothesis is a classical and notable explanation for the relationship between creativity and intelligence. However, few empirical examinations of this theory exist, and the results are inconsistent. To test this hypothesis, this study investigated the relationship between divergent thinking (DT) and intelligence with a sample of 568 Chinese children aged between 11 and 13 years old using testing and questionnaire methods. The study focused on the breakpoint of intelligence and the moderation effect of openness on the relationship between intelligence and DT. The findings were as follows: (1) a breakpoint at the intelligence quotient (IQ) of 109.20 when investigating the relationship between either DT fluency or DT flexibility and intelligence. Another breakpoint was detected at the IQ of 116.80 concerning the correlation between originality and intelligence. The breakpoint of the relation between the composite score of creativity and intelligence occurred at the IQ of 110.10. (2) Openness to experience had a moderating effect on the correlation between the indicators of creativity and intelligence under the breakpoint. Above this point, however, the effect was not significant. The results suggested a relationship between DT and intelligence among Chinese children, which conforms to the threshold hypothesis. Besides, it remains necessary to explore the personality factors accounting for individual differences in the relationship between DT and intelligence.

Retinitis pigmentosa (RP) is an inherited blinding disease characterized by progressive loss of retinal photo-receptors. There are numerous rodent models of retinal degeneration, but most are poor platforms for interventions that will translate into clinical practice. The rabbit possesses a number of desirable qualities for a model of retinal disease including a large eye and an existing and substantial knowledge base in retinal circuitry, anatomy, and ophthalmology. We have analyzed degeneration, remodeling, and reprogramming in a rabbit model of retinal degeneration, expressing a rhodopsin proline 347 to leucine transgene in a TgP347L rabbit as a powerful model to study the pathophysiology and treatment of retinal degeneration. We show that disease progression in the TgP347L rabbit closely tracks human cone-sparing RP, including the coneassociated preservation of bipolar cell signaling and triggering of reprogramming. The relatively fast disease progression makes the TgP347L rabbit an excellent model for gene therapy, cell biological intervention, progenitor cell transplantation, surgical interventions, and bionic prosthetic studies.

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Retinoblastoma (RB) is an aggressive eye cancer of infancy and childhood with high mortality. Studies have shown that long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) is closely related to the progression of multiple cancers. However, its role in RB remains unknown. This study aimed to investigate the role and underlying mechanism of NEAT1 in RB. We first detected the expression of NEAT1 in human RB tissues and cell lines. The effects of NEAT1 on the proliferation, migration, and apoptosis of RB cells were analyzed by loss‐of‐function. The underlying mechanism of NEAT1 in RB was mainly focused on the microRNA 204/C‐X‐C chemokine receptor type 4 (miR‐204/CXCR4) axis. In addition, the role and mechanism of NEAT1 in RB were further evaluated in a mouse xenograft tumor model. We found NEAT1 and CXCR4 expression levels were elevated, whereas miR‐204 expression was decreased in RB tissues and cells. Downregulation of NEAT1 significantly decreased the proliferation and migration but promoted the apoptosis of RB cells. NEAT1 functioned as a competing endogenous RNA for miR‐204 to regulate CXCR4 expression. Knockdown of NEAT1 suppressed the tumor volume, tumor weight, and CXCR4 expression, whereas increased miR‐204 expression in mice. In conclusion, NEAT1 promotes the development of RB via miR‐204/CXCR4 axis, which provides a new target for the treatment of RB disease.

Background: Chronic rhinosinusitis (CRS) is characterized by persistent symptomatic inflammation of the nasal passage and sinus mucosa. Various microRNAs (miRs) have been implicated in CRS. Hence, the current study was conducted to explore the effect of microRNA-761 (miR-761) on remodeling of nasal mucosa and epithelial-mesenchymal transition (EMT).Methods: Bioinformatics analysis was initially performed to predict the differentially expressed genes (DEGs) associated with CRS. Gene targeting relationship between miR-761 and lipocalin 2 (LCN2) was analyzed by bioinformatics analysis and verified using dual-luciferase reporter gene assay. Histopathological analyses of the nasal mucosa tissues were conducted via hematoxylin-eosin (HE) and alcian blue (AB)-periodic acid Schiff (PAS) staining. ELISA was employed to determine the IL-8 and MMP-9 levels. To define downstream pathway of miR-761, levels of proteins related to LCN2/Twist1 signaling pathway were assessed. Additionally, the effects of miR-761 on EMT, proliferation, and apoptosis were determined.Results: LCN2 was highly expressed in CRS. LCN2 was a target of miR-761. miR-761 overexpression or LCN2 silencing decreased IL-8 and MMP-9 levels and morphological changes in nasal epithelial tissue from CRS mice. Overexpressed miR-761 or silenced LCN2 decreased the expression of LCN2 and Twist1, indicating LCN2/Twist1 signaling pathway was inactivated. Moreover, miR-761 overexpression or LCN2 silencing reduced the expression of N-cadherin and vimentin, while increased that of E-cadherin, suggesting inhibition of EMT. Furthermore, miR-761 overexpression or LCN2 silencing promoted cell proliferation and inhibited cell apoptosis in CRS.Conclusion: Taken together, miR-761 suppressed the remodeling of nasal mucosa through inhibition of LCN2 and the LCN2/Twist1 signaling pathway.