Using Virtual Reality Simulation for Screening Brief Intervention and Referral to Treatment.

BACKGROUND: This study examined the effects of virtual reality on students' confidence and knowledge in Screening, Brief Intervention, and Referral to Treatment (SBIRT), and understanding of substance use disorders (SUDs) in mental health and primary care settings. METHOD: Using a pre- and postdesign, questionnaires were distributed before, immediately after, and 3 months after the simulation. RESULTS: Data analysis revealed significant increases in SBIRT characteristics, screening tools, and alcohol consumption guidelines from pre- to postsimulation (p < .05) among the participants (n = 380). Confidence levels improved significantly (p < .001), with no notable difference between post-simulation and follow-up surveys. CONCLUSION: Simulation training with structured prebriefing and debriefing sessions facilitated the application of learned skills during the simulation, boosting students' self-efficacy and readiness. [J Nurs Educ. 2024;63(7):453-459.].

Crosstalk between chromatin, chromosomes, and epigenetics.

The International Asilomar Chromatin, Chromosomes, and Epigenetics Conference was held online from 8 to 10 December 2022. Topics of this year's conference included chromosome dysregulation, genome integrity, nuclear organization, regulation of chromatin, epigenetics, transcription, and gene regulation in cell differentiation and disease. The meeting featured four keynote speakers, including Yamini Dalal (National Cancer Institute, USA), Meaghan Jones (University of Manitoba, Canada), Pedro Rocha (National Institute of Child Health and Human Development, USA), and Vincent Pasque (University of Leuven, Belgium). The meeting brought together scientists at all career stages to present and discuss their work in the fields of chromatin and epigenetics.

The ChIP-Exo Method to Identify Genomic Locations of DNA-Binding Proteins at Near Single Base-Pair Resolution.

Chromatin immunoprecipitation (ChIP) is a technique to determine whether a protein interacts with a specific DNA sequence. ChIP-sequencing (ChIP-seq) is one of the most widely used methods to identify genome-wide DNA-binding sites of nuclear proteins. Here, we describe the ChIP-exo method, which is a refined version of ChIP-seq combined with lambda exonuclease digestion. ChIP-exo can identify genomic locations of DNA-binding proteins at a near single base-pair (bp) resolution. It removes most of the background DNA signals. ChIP-exo has emerged as a powerful technique to study the genome-wide organization of DNA-binding proteins.

Extended intergenic DNA contributes to neuron-specific expression of neighboring genes in the mammalian nervous system.

Mammalian genomes comprise largely intergenic noncoding DNA with numerous cis-regulatory elements. Whether and how the size of intergenic DNA affects gene expression in a tissue-specific manner remain unknown. Here we show that genes with extended intergenic regions are preferentially expressed in neural tissues but repressed in other tissues in mice and humans. Extended intergenic regions contain twice as many active enhancers in neural tissues compared to other tissues. Neural genes with extended intergenic regions are globally co-expressed with neighboring neural genes controlled by distinct enhancers in the shared intergenic regions. Moreover, generic neural genes expressed in multiple tissues have significantly longer intergenic regions than neural genes expressed in fewer tissues. The intergenic regions of the generic neural genes have many tissue-specific active enhancers containing distinct transcription factor binding sites specific to each neural tissue. We also show that genes with extended intergenic regions are enriched for neural genes only in vertebrates. The expansion of intergenic regions may reflect the regulatory complexity of tissue-type-specific gene expression in the nervous system.

Cellular secretion and cytotoxicity of transthyretin mutant proteins underlie late-onset amyloidosis and neurodegeneration.

Transthyretin amyloidosis (ATTR) is a progressive life-threatening disease characterized by the deposition of transthyretin (TTR) amyloid fibrils. Several pathogenic variants have been shown to destabilize TTR tetramers, leading to aggregation of misfolded TTR fibrils. However, factors that underlie the differential age of disease onset amongst amyloidogenic TTR variants remain elusive. Here, we examined the biological properties of various TTR mutations and found that the cellular secretory pattern of the wild-type (WT) TTR was similar to those of the late-onset mutant (Ala97Ser, p. Ala117Ser), stable mutant (Thr119Met, p. Thr139Met), early-onset mutant (Val30Met, p. Val50Met), but not in the unstable mutant (Asp18Gly, p. Asp38Gly). Cytotoxicity assays revealed their toxicities in the order of Val30Met > Ala97Ser > WT > Thr119Met in neuroblastoma cells. Surprisingly, while early-onset amyloidogenic TTR monomers (M-TTRs) are retained by the endoplasmic reticulum quality control (ERQC), late-onset amyloidogenic M-TTRs can be secreted extracellularly. Treatment of thapsigargin (Tg) to activate the unfolded protein response (UPR) alleviates Ala97Ser M-TTR secretion. Interestingly, Ala97Ser TTR overexpression in Drosophila causes late-onset fast neurodegeneration and a relatively short lifespan, recapitulating human disease progression. Our study demonstrates that the escape of TTR monomers from the ERQC may underlie late-onset amyloidogenesis in patients and suggests that targeting ERQC could mitigate late-onset ATTR.

Contributions of Animal Models to the Mechanisms and Therapies of Transthyretin Amyloidosis.

Transthyretin amyloidosis (ATTR amyloidosis) is a fatal systemic disease caused by amyloid deposits of misfolded transthyretin, leading to familial amyloid polyneuropathy and/or cardiomyopathy, or a rare oculoleptomeningeal amyloidosis. A good model system that mimic the disease phenotype is crucial for the development of drugs and treatments for this devastating degenerative disorder. The present models using fruit flies, worms, rodents, non-human primates and induced pluripotent stem cells have helped researchers understand important disease-related mechanisms and test potential therapeutic options. However, the challenge of creating an ideal model still looms, for these models did not recapitulates all symptoms, particularly neurological presentation, of ATTR amyloidosis. Recently, knock-in techniques was used to generate two humanized ATTR mouse models, leading to amyloid deposition in the nerves and neuropathic manifestation in these models. This review gives a recent update on the milestone, progress, and challenges in developing different models for ATTR amyloidosis research.