Functional loss of TDP-43, an RNA binding protein genetically and pathologically linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leads to the inclusion of cryptic exons in hundreds of transcripts during disease. Cryptic exons can promote the degradation of affected transcripts, deleteriously altering cellular function through loss-of-function mechanisms. Here, we show that mRNA transcripts harboring cryptic exons generated de novo proteins in TDP-43-depleted human iPSC-derived neurons in vitro, and de novo peptides were found in cerebrospinal fluid (CSF) samples from patients with ALS or FTD.
View Article and Find Full Text PDFFunctional loss of TDP-43, an RNA-binding protein genetically and pathologically linked to ALS and FTD, leads to inclusion of cryptic exons in hundreds of transcripts during disease. Cryptic exons can promote degradation of affected transcripts, deleteriously altering cellular function through loss-of-function mechanisms. However, the possibility of protein synthesis from cryptic exon transcripts has not been explored.
View Article and Find Full Text PDFHuman induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.
View Article and Find Full Text PDFThe past decade has seen an enormous increase in the number and breadth of imaging techniques developed for analysis in many industries, including pharmaceuticals, food, and especially biomedicine. Rather than accept single-dimensional forms of information, users now demand multidimensional assessment of samples. High specificity and the need for little or no sample preparation make Raman imaging a highly attractive analytical technique and provide motivation for continuing advances in its supporting technology and utilization.
View Article and Find Full Text PDFRaman spectroscopy is being evaluated as a candidate technology for waterborne pathogen detection. We have investigated the impact of key experimental and background interference parameters on the bacterial species level identification performance of Raman detection. These parameters include laser-induced photodamage threshold, composition of water matrix, and organism aging in water.
View Article and Find Full Text PDFPurpose: This study was conducted to evaluate the feasibility of using Raman chemical imaging (i.e., Raman imaging microspectroscopy) to establish chemical identity, particle size and particle size distribution (PSD) for a representative corticosteroid in aqueous nasal spray suspension formulations.
View Article and Find Full Text PDFAn optical detection method, Raman chemical imaging spectroscopy (RCIS), is reported, which combines Raman spectroscopy, fluorescence spectroscopy, and digital imaging. Using this method, trace levels of biothreat organisms are detected in the presence of complex environmental backgrounds without the use of amplification or enhancement techniques. RCIS is reliant upon the use of Raman signatures and automated recognition algorithms to perform species-level identification.
View Article and Find Full Text PDFChemical imaging technology is a rapid examination technique that combines molecular spectroscopy and digital imaging, providing information on morphology, composition, structure, and concentration of a material. Among many other applications, chemical imaging offers an array of novel analytical testing methods, which limits sample preparation and provides high-quality imaging data essential in the detection of latent fingerprints. Luminescence chemical imaging and visible absorbance chemical imaging have been successfully applied to ninhydrin, DFO, cyanoacrylate, and luminescent dye-treated latent fingerprints, demonstrating the potential of this technology to aid forensic investigations.
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