Publications by authors named "Ryan Szeto"

The mammalian cerebral cortex shows functional specialization into regions with distinct neuronal compositions, most strikingly in the human brain, but little is known in about how cellular lineages shape cortical regional variation and neuronal cell types during development. Here, we use somatic single nucleotide variants (sSNVs) to map lineages of neuronal sub-types and cortical regions. Early-occurring sSNVs rarely respect Brodmann area (BA) borders, while late-occurring sSNVs mark neuron-generating clones with modest regional restriction, though descendants often dispersed into neighboring BAs.

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Prenatal alcohol exposure is the foremost preventable etiology of intellectual disability and leads to a collection of diagnoses known as Fetal Alcohol Spectrum Disorders (FASD). Alcohol (EtOH) impacts diverse neural cell types and activity, but the precise functional pathophysiological effects on the human fetal cerebral cortex are unclear. Here, we used human cortical organoids to study the effects of EtOH on neurogenesis and validated our findings in primary human fetal neurons.

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The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which was rapidly declared a pandemic by the World Health Organization (WHO). Early clinical symptomatology focused mainly on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are now well-documented.

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Transcription Factor 4 (TCF4) has been associated with autism, schizophrenia, and other neuropsychiatric disorders. However, how pathological TCF4 mutations affect the human neural tissue is poorly understood. Here, we derive neural progenitor cells, neurons, and brain organoids from skin fibroblasts obtained from children with Pitt-Hopkins Syndrome carrying clinically relevant mutations in TCF4.

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Maricic . performed an undisclosed in silico–only whole-exome sequencing analysis of our data and found genomic alterations previously undetected in some clones. Some of the predicted alterations, if true, could change the original genotype of the clones.

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The measurement of yield stress and shear thinning flow behavior of slurries formed from unpretreated corn stover at solids loadings of 100-300 g/L provides a key metric for the ability to move, pump, and mix this lignocellulosic slurry, particularly since corn stover slurries represent a major potential feedstock for biorefineries. This study compared static yield stress values and flow hysteresis of corn stover slurries of 100, 150, 200, 250, and 300 g/L, after these slurries were formed by adding pellets to a cellulase enzyme solution (Celluclast 1.5 L) in a fed-batch manner.

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The movement of solid material into and between unit operations within a biorefinery is a bottleneck in reaching design capacity, with formation of biomass slurries needed to introduce feedstock. Corn stover slurries have been achieved from dilute acid, pretreated materials resulting in slurry concentrations of up to about 150 g/L, above which flowability is compromised. We report a new strategy to liquefy corn stover at higher solids concentration (300 g/L) by initially cooking it with the enzyme mimetic maleic acid at 40 mM and 150 °C.

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Early-onset epileptic encephalopathies are severe disorders often associated with specific genetic mutations. In this context, the CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by early-onset seizures, intellectual delay, and motor dysfunction. Although crucial for proper brain development, the precise targets of CDKL5 and its relation to patients' symptoms are still unknown.

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CO and O gas permeability are paramount concerns in food packaging. Here, the permeability of cellulose nanocrystals (CNCs) and polyvinyl alcohol (PVA) coatings was explored as it relates to varied CNC content. Specifically, this work focuses on the role of PVA in rheology and barrier performance of the CNC films.

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Article Synopsis
  • The protein-coding gene neuro-oncological ventral antigen 1 (NOVA1) is crucial for brain development and differs between modern humans and our extinct relatives, the Neanderthals and Denisovans.
  • Researchers used genome editing to introduce an ancient version of this gene into modern human cells and studied its effects on brain organoids.
  • The archaic version of NOVA1 slowed neural development and changed the complexity and electrical properties of the organoids, suggesting that human-specific changes to this gene may have influenced our evolution.
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The human transcription factor 4 gene (TCF4) encodes a helix-loop-helix transcription factor widely expressed throughout the body and during neural development. Mutations in TCF4 cause a devastating autism spectrum disorder known as Pitt-Hopkins syndrome, characterized by a range of aberrant phenotypes including severe intellectual disability, absence of speech, delayed cognitive and motor development, and dysmorphic features. Moreover, polymorphisms in TCF4 have been associated with schizophrenia and other psychiatric and neurological conditions.

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Gene expression comprises a diverse array of enzymes, proteins, non-coding transcripts, and cellular structures to guide the transfer of genetic information to its various final products. In the brain, the coordination among genes, or lack thereof, characterizes individual brain regions, mediates a variety of brain-related disorders, and brings light to fundamental differences between species. RNA processing, occurring between transcription and translation, controls an essential portion of gene expression through splicing, editing, localization, stability, and interference.

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A comprehensive review of the literature shows that enzyme hydrolysis efficiency decreases with increased solids loadings at constant enzyme:cellulose ratios for pretreated lignocellulosic substrates. In seeking a mechanistic explanation for this phenomenon, we found that a nitrogen atmosphere enhances enzyme hydrolysis and minimizes the decrease in glucose yields as solids loadings are increased in an agitated bioreactor. For liquid hot water pretreated corn stover, at solids loadings of both 100 and 200 g/L and hydrolyzed for 72 hr in a 1 L bioreactor at pH 5.

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In this work, we explore video frame inpainting, a task that lies at the intersection of general video inpainting, frame interpolation, and video prediction. Although our problem can be addressed by applying methods from other video interpolation or extrapolation tasks, doing so fails to leverage the additional context information that our problem provides. To this end, we devise a method specifically designed for video frame inpainting that is composed of two modules: a bidirectional video prediction module and a temporally-aware frame interpolation module.

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Graphene has been publicized as the game changing material of this millennium. To this day, scalable production leading to exceptional material properties has been difficult to attain. Most methods require harsh chemicals, which result in destroying the graphene surface.

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