Recapitulation of Perturbed Striatal Gene Expression Dynamics of Donors' Brains With Ventral Forebrain Organoids Derived From the Same Individuals With Schizophrenia.

OBJECTIVE: Schizophrenia is a brain disorder that originates during neurodevelopment and has complex genetic and environmental etiologies. Despite decades of clinical evidence of altered striatal function in affected patients, studies examining its cellular and molecular mechanisms in humans are limited. To explore neurodevelopmental alterations in the striatum associated with schizophrenia, the authors established a method for the differentiation of induced pluripotent stem cells (iPSCs) into ventral forebrain organoids (VFOs). METHODS: VFOs were generated from postmortem dural fibroblast-derived iPSCs of four individuals with schizophrenia and four neurotypical control individuals for whom postmortem caudate genotypes and transcriptomic data were profiled in the BrainSeq neurogenomics consortium. Individuals were selected such that the two groups had nonoverlapping schizophrenia polygenic risk scores (PRSs). RESULTS: Single-cell RNA sequencing analyses of VFOs revealed differences in developmental trajectory between schizophrenia and control individuals in which inhibitory neuronal cells from the patients exhibited accelerated maturation. Furthermore, upregulated genes in inhibitory neurons in schizophrenia VFOs showed a significant overlap with upregulated genes in postmortem caudate tissue of individuals with schizophrenia compared with control individuals, including the donors of the iPSC cohort. CONCLUSIONS: The findings suggest that striatal neurons derived from high-PRS individuals with schizophrenia carry abnormalities that originated during early brain development and that the VFO model can recapitulate disease-relevant cell type-specific neurodevelopmental phenotypes in a dish.

Coupled Urban Change and Natural Hazard Consequence Model for Community Resilience Planning.

This paper presents a new coupled urban change and hazard consequence model that considers population growth, a changing built environment, natural hazard mitigation planning, and future acute hazards. Urban change is simulated as an agent-based land market with six agent types and six land use types. Agents compete for parcels with successful bids leading to changes in both urban land use-affecting where agents are located-and structural properties of buildings-affecting the building's ability to resist damage to natural hazards. IN-CORE, an open-source community resilience model, is used to compute damages to the built environment. The coupled model operates under constraints imposed by planning policies defined at the start of a simulation. The model is applied to Seaside, Oregon, a coastal community in the North American Pacific Northwest subject to seismic-tsunami hazards emanating from the Cascadia Subduction Zone. Ten planning scenarios are considered including caps on the number of vacation homes, relocating community assets, limiting new development, and mandatory seismic retrofits. By applying this coupled model to the testbed community, we show that: (a) placing a cap on the number of vacation homes results in more visitors in damaged buildings, (b) that mandatory seismic retrofits do not reduce the number of people in damaged buildings when considering population growth, (c) polices diverge beyond year 10 in the model, indicating that many policies take time to realize their implications, and (d) the most effective policies were those that incorporated elements of both urban planning and enforced building codes.

Structural health monitoring data collected during construction of a mass-timber building with a data platform for analysis.

The George W. Peavy Forest Science Complex, or "Peavy Hall," is a mass-timber university building that is the subject of a structural health monitoring (SHM) program to create a comprehensive building performance dataset. The building substructure consists of cross-laminated timber (CLT)-concrete composite floors, a mass plywood panel (MPP) roof system, and the world's first application of CLT post-tensioned (PT) self-centering shear walls. This document reports on static and hygrothermal data collected during the final ten months of building construction that were used to validate a proposed methodological approach to SHM for mass-timber buildings under construction, described in A Methodological Approach for Structural Health Monitoring of Mass-Timber Buildings Under Construction[1]. These data, available in the repository at https://osf.io/jdz6y/, include wood moisture content of CLT, MPP, and glulam structural components, horizontal and vertical displacements of axially loaded CLT panels, tension loss of PT steel rods within CLT self-centering walls, and indoor and outdoor environmental conditions such as temperature, relative humidity, rain quantities, wind speeds, as well as wind directions. Additionally, data figures and analysis coding files are included in the repository to further define processes and allow for potential use of the analysis tools for similar projects.