A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brai

A Computational Pipeline for High- Throughput Discovery of cis-Regulatory Noncoding RNA in Prokaryotes

Noncoding RNAs (ncRNAs) are important functional RNAs that do not code for proteins. We present a highly efficient computational pipeline for discovering cis-regulatory ncRNA motifs de novo. The pipeline differs from previous methods in that it is structure-oriented, does not require a multiple-sequence alignment as input, and is capable of detecting RNA motifs with low sequence conservation. We also integrate RNA motif prediction with RNA homolog search, which improves the quality of the RNA motifs significantly. Here, we report the results of applying this pipeline to Firmicute bacteria. Our top-ranking motifs include most known Firmicute elements found in the RNA family database (Rfam). Comparing our motif models with Rfam's hand-curated motif models, we achieve high accuracy in both membership prediction and base-pair–level secondary structure prediction (at least 75% average sensitivity and specificity on both tasks). Of the ncRNA candidates not in Rfam, we find compelling evidence that some of them are functional, and analyze several potential ribosomal protein leaders in depth

Genome engineering of isogenic human ES cells to model autism disorders.

Isogenic pluripotent stem cells are critical tools for studying human neurological diseases by allowing one to study the effects of a mutation in a fixed genetic background. Of particular interest are the spectrum of autism disorders, some of which are monogenic such as Timothy syndrome (TS); others are multigenic such as the microdeletion and microduplication syndromes of the 16p11.2 chromosomal locus. Here, we report engineered human embryonic stem cell (hESC) lines for modeling these two disorders using locus-specific endonucleases to increase the efficiency of homology-directed repair (HDR). We developed a system to: (1) computationally identify unique transcription activator-like effector nuclease (TALEN) binding sites in the genome using a new software program, TALENSeek, (2) assemble the TALEN genes by combining golden gate cloning with modified constructs from the FLASH protocol, and (3) test the TALEN pairs in an amplification-based HDR assay that is more sensitive than the typical non-homologous end joining assay. We applied these methods to identify, construct, and test TALENs that were used with HDR donors in hESCs to generate an isogenic TS cell line in a scarless manner and to model the 16p11.2 copy number disorder without modifying genomic loci with high sequence similarity

A Marfan syndrome gene expression phenotype in cultured skin fibroblasts

<p>Abstract</p> <p>Background</p> <p>Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms.</p> <p>Results</p> <p>We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR.</p> <p>Conclusion</p> <p>Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value < 3 × 10^-6under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status). An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater.</p

Quantum dot passivation of halide perovskite films with reduced defects, suppressed phase segregation, and enhanced stability

Structural defects are ubiquitous for polycrystalline perovskite films, compromising device performance and stability. Herein, a universal method is developed to overcome this issue by incorporating halide perovskite quantum dots (QDs) into perovskite polycrystalline films. CsPbBr3 QDs are deposited on four types of halide perovskite films (CsPbBr3, CsPbIBr2, CsPbBrI2, and MAPbI3) and the interactions are triggered by annealing. The ions in the CsPbBr3 QDs are released into the thin films to passivate defects, and concurrently the hydrophobic ligands of QDs self-assemble on the film surfaces and grain boundaries to reduce the defect density and enhance the film stability. For all QD-treated films, PL emission intensity and carrier lifetime are significantly improved, and surface morphology and composition uniformity are also optimized. Furthermore, after the QD treatment, light-induced phase segregation and degradation in mixed-halide perovskite films are suppressed, and the efficiency of mixed-halide CsPbIBr2 solar cells is remarkably improved to over 11% from 8.7%. Overall, this work provides a general approach to achieving high-quality halide perovskite films with suppressed phase segregation, reduced defects, and enhanced stability for optoelectronic applications.Peer ReviewedPostprint (author's final draft

Perovskite quantum dot solar cells fabricated from recycled lead-acid battery waste

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Materials Letters, copyright © 2021 American Chemical Societ, after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsmaterialslett.1c00592.A cost-effective and environmentally friendly Pb source is a prerequisite for achieving large-scale, low-cost perovskite photovoltaic devices. Currently, the commonly used method to prepare the lead source is based on a fire smelting process, requiring a high temperature of more than 1000 °C, which results in environmental pollution. Spent car lead acid batteries are an environmentally hazardous waste; however, they can alternatively serve as an abundant and inexpensive Pb source. Due to “self-purification”, quantum dots feature a high tolerance of impurities in the precursor since the impurities tend to be expelled from the small crystalline cores during colloidal nucleation. Herein, PbI2 recycled from spent lead acid batteries via a facile low-temperature solution process is used to synthesize CsPbI3 quantum dots, which simultaneously brings multiple benefits including (1) avoiding pollution originating from the fire smelting process; (2) recycling the Pb waste from batteries; and (3) synthesizing high-quality quantum dots. The resulting CsPbI3 quantum dots have photophysical properties such as PLQY and carrier lifetimes on par with those synthesized from the commercial PbI2 due to expelling of the impurity Na atoms. The resulting solar cells deliver comparable power conversion efficiencies: 14.0% for the cells fabricated using recycled PbI2 and 14.7% for the cells constructed using commercial PbI2. This work paves a new and feasible path to applying recycled Pb sources in perovskite photovoltaics.Peer ReviewedPostprint (author's final draft