Consistent self-organized emergence of hyaline cartilage in hiPSC-derived multi-tissue organoids.

Existing protocols for in vitro hyaline cartilage production utilizing human induced pluripotent stem cells (hiPSCs) have several challenges including a complex culturing process that uses undefined culture media, phenotypic instability, and batch-to-batch variability of the cell product. Here, our primary objective is to describe a simple, xeno- and feeder-free protocol for the generation of hyaline cartilage utilizing multi-tissue organoids (MTOs). We investigated gene regulatory networks during hiPSC-MTO differentiation using RNA sequencing and bioinformatics analyses, as well as histological and immunohistochemical methods.

Detection and Decontamination of Chronic Wasting Disease Prions during Venison Processing.

Prion diseases, including chronic wasting disease (CWD), are caused by prions, which are misfolded aggregates of normal cellular prion protein. Prions possess many characteristics that distinguish them from conventional pathogens, in particular, an extraordinary recalcitrance to inactivation and a propensity to avidly bind to surfaces. In middle to late stages of CWD, prions begin accumulating in cervid muscle tissues.

Multifaceted Role of Specialized Neuropeptide-Intensive Neurons on the Selective Vulnerability to Alzheimer's Disease in the Human Brain.

Regarding Alzheimer's disease (AD), specific neuronal populations and brain regions exhibit selective vulnerability. Understanding the basis of this selective neuronal and regional vulnerability is essential to elucidate the molecular mechanisms underlying AD pathology. However, progress in this area is currently hindered by the incomplete understanding of the intricate functional and spatial diversity of neuronal subtypes in the human brain.

QuICSeedR: an R package for analyzing fluorophore-assisted seed amplification assay data.

Motivation: Fluorophore-assisted seed amplification assays (F-SAAs), such as real-time quaking-induced conversion (RT-QuIC) and fluorophore-assisted protein misfolding cyclic amplification (F-PMCA), have become indispensable tools for studying protein misfolding in neurodegenerative diseases. However, analyzing data generated by these techniques often requires complex and time-consuming manual processes. In addition, the lack of standardization in F-SAA data analysis presents a significant challenge to the interpretation and reproducibility of F-SAA results across different laboratories and studies.

Prion forensics: a multidisciplinary approach to investigate CWD at an illegal deer carcass disposal site.

Infectious prions are resistant to degradation and remain infectious in the environment for several years. Chronic wasting disease (CWD) has been detected in cervids inhabiting North America, the Nordic countries, and South Korea. CWD-prion spread is partially attributed to carcass transport and disposal.

Multifaceted impact of specialized neuropeptide-intensive neurons on the selective vulnerability in Alzheimer's disease.

Introduction: Widespread disruption of neuropeptide (NP) networks in Alzheimer's disease (AD) and disproportionate absence of neurons expressing igh P-roducing, coined as HNP neurons, have been reported for the entorhinal cortex (EC) of AD brains. Hypothesizing that functional features of HNP neurons are involved in the early pathogenesis of AD, we aim to understand the molecular mechanisms underlying these observations.

Methods: Multiscale and spatiotemporal transcriptomic analysis was used to investigate AD-afflicted and healthy brains.

Nanoparticle-Enhanced RT-QuIC (Nano-QuIC) Diagnostic Assay for Misfolded Proteins.

Misfolded proteins associated with various neurodegenerative diseases often accumulate in tissues or circulate in biological fluids years before the clinical onset, thus representing ideal diagnostic targets. Real-time quaking-induced conversion (RT-QuIC), a protein-based seeded-amplification assay, holds great potential for early disease detection, yet challenges remain for routine diagnostic application. Chronic Wasting Disease (CWD), associated with misfolded prion proteins of cervids, serves as an ideal model for evaluating new RT-QuIC methodologies.

Standardization of Data Analysis for RT-QuIC-Based Detection of Chronic Wasting Disease.

Chronic wasting disease (CWD) is a disease affecting cervids and is caused by prions accumulating as pathogenic fibrils in lymphoid tissue and the central nervous system. Approaches for detecting CWD prions historically relied on antibody-based assays. However, recent advancements in protein amplification technology provided the foundation for a new class of CWD diagnostic tools.

Single-cell sequencing of entorhinal cortex reveals widespread disruption of neuropeptide networks in Alzheimer's disease.

Introduction: Abnormalities of neuropeptides (NPs) that play important roles in modulating neuronal activities are commonly observed in Alzheimer's disease (AD). We hypothesize that NP network disruption is widespread in AD brains.

Methods: Single-cell transcriptomic data from the entorhinal cortex (EC) were used to investigate the NP network disruption in AD.

A field-deployable diagnostic assay for the visual detection of misfolded prions.

Diagnostic tools for the detection of protein-misfolding diseases (i.e., proteopathies) are limited.

COMPARISON OF CHRONIC WASTING DISEASE DETECTION METHODS AND PROCEDURES: IMPLICATIONS FOR FREE-RANGING WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) SURVEILLANCE AND MANAGEMENT.

Throughout North America, chronic wasting disease (CWD) has emerged as perhaps the greatest threat to wild cervid populations, including white-tailed deer (WTD; Odocoileus virginianus). White-tailed deer are the most sought-after big game species across North America with populations of various subspecies in nearly all Canadian provinces, the contiguous US, and Mexico. Documented CWD cases have dramatically increased across the WTD range since the mid-1990s, including in Minnesota, US.

Primate-specific retrotransposons and the evolution of circadian networks in the human brain.

The circadian rhythm of the human brain is attuned to sleep-wake cycles that entail global alterations in neuronal excitability. This periodicity involves a highly coordinated regulation of gene expression. A growing number of studies are documenting a fascinating connection between primate-specific retrotransposons (Alu elements) and key epigenetic regulatory processes in the primate brain.

RT-QuIC detection of CWD prion seeding activity in white-tailed deer muscle tissues.

Chronic wasting disease (CWD) is a prion disease circulating in wild and farmed cervid populations throughout North America (United States and Canada), Europe (Finland, Norway, Sweden), and South Korea. CWD is a long-term threat to all cervid populations and to cervid hunting heritage, with the potential to cause substantial economic losses across multiple sectors. In North America, hunting and farming industries focused on the processing and consumption of white-tailed deer (WTD) venison are particularly vulnerable to CWD prion contamination, as millions of WTD are consumed annually.

Alu retrotransposons and COVID-19 susceptibility and morbidity.

SARS-CoV-2 has spread rapidly across the world and is negatively impacting the global human population. COVID-19 patients display a wide variety of symptoms and clinical outcomes, including those attributed to genetic ancestry. Alu retrotransposons have played an important role in human evolution, and their variants influence host response to viral infection.

Shedding and stability of CWD prion seeding activity in cervid feces.

CWD is an emergent prion disease that now affects cervid species on three continents. CWD is efficiently spread in wild and captive populations, likely through both direct animal contact and environmental contamination. Here, by longitudinally assaying in feces of CWD-exposed white-tailed deer by RT-QuIC, we demonstrate fecal shedding of prion seeding activity months before onset of clinical symptoms and continuing throughout the disease course.