Modelling human neurodevelopmental pathologies in vitro: a focus on neural loss and Down syndrome

Relevant and reproducible in vitro models of human neural injury and disease are needed to investigate neurodevelopmental pathology and damage response. This is particularly pertinent for pathologies with poor translation from animal models, including hypoxic-ischaemic injury (HI) and Down syndrome (DS). DS is a multi-systemic developmental disorder and the most common genetic form of mental disability. In vivo models of DS are limited by species-specific chromosomal and neurodevelopmental differences. Perinatal HI is the leading cause of neonatal mortality and neurological disability. Although several potential treatments have shown efficacy in animal models of HI, this success has not translated to human clinical trials. This work aims to develop and validate improved in vitro methods to investigate human neurodevelopmental damage and disease, with a focus on HI and DS. To better represent tissue architecture, 3-dimensional (3D) hydrogel cultures of human neural stem cells (hNSCs) were developed and optimised. Injury models and viability readouts of HI, calcium-dependent and oxidative stress-induced cell death were established in 2D and 3D cultures. Significantly, neural gene expression and injury response were altered in 3D cultures compared to 2D, emphasising the importance of culture architecture for in vitro studies. DS- and control-induced pluripotent cell (iPSC) lines were generated, characterised, and differentiated towards neural progenitor cells (NPCs). Fewer NPCs were produced by DS-iPSCs than control-iPSCs, reflecting both a reduced rate of NPC proliferation and increased NPC death. DS-neurons displayed abnormal morphology, reduced Ca 2+ activity, and altered gene expression. Both 2D and 3D cultures of DS-NPCs displayed increased susceptibility to oxidative stress, whereas DS-astrocytes displayed a decreased vulnerability to oxidative stress and Ca 2+-dependent injury. These findings support the hypotheses that DS-NPC proliferative impairment and susceptibility to oxidative stress contribute to DS neurodevelopmental impairments. Further, these results demonstrate a proof-of-principle for a 3D in vitro model system for the investigation of neural cell injury and neurodevelopmental disorder

Social Media and Marketing as a Means of Planning and Promoting the 2022 Camp PolyHacks Hackathon

The recruitment of attendees and promotion of Camp PolyHacks, an annual Hackathon hosted by Cal Poly, required marketing strategies which were informed by relevant communication theories applied to event marketing campaign strategies. The theories utilized included Social Marketing Theory (SMT), Uncertainty Reduction Theory (URT), Consistency Theory (CT), and elements of persuasion and visual communication. The marketing strategies used by the Camp PolyHacks 2022 Marketing and Social Media team included social media marketing in the form of Instagram posts, stories, and direct messages, and external marketing in the form of presentations, emails, booths, and posters. This paper examines the utility of these marketing strategies, how they were informed by communication theories, and why they are valuable for future applications. The evaluation of the marketing tactics used during the Camp PolyHacks recruitment period offers insight into best practices for recruiting 100 student participants to attend a community and university based event in San Luis Obispo. An appendix at the end of the paper will provide a sample of the tools and content that were used throughout the marketing process through social media and external marketing

PolyQ length-dependent metabolic alterations and DNA damage drive human astrocyte dysfunction in Huntington's disease

Huntington's Disease (HD) is a neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the Huntingtin gene. Astrocyte dysfunction is known to contribute to HD pathology, however our understanding of the molecular pathways involved is limited. Transcriptomic analysis of patient-derived PSC (pluripotent stem cells) astrocyte lines revealed that astrocytes with similar polyQ lengths shared a large number of differentially expressed genes (DEGs). Notably, weighted correlation network analysis (WGCNA) modules from iPSC derived astrocytes showed significant overlap with WGCNA modules from two post-mortem HD cohorts. Further experiments revealed two key elements of astrocyte dysfunction. Firstly, expression of genes linked to astrocyte reactivity, as well as metabolic changes were polyQ length-dependent. Hypermetabolism was observed in shorter polyQ length astrocytes compared to controls, whereas metabolic activity and release of metabolites were significantly reduced in astrocytes with increasing polyQ lengths. Secondly, all HD astrocytes showed increased DNA damage, DNA damage response and upregulation of mismatch repair genes and proteins. Together our study shows for the first time polyQ-dependent phenotypes and functional changes in HD astrocytes providing evidence that increased DNA damage and DNA damage response could contribute to HD astrocyte dysfunction

Multi-Component Resilience Assessment Framework for a Supply Chain System

13-C-AJFE-WaSU-016This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) license https://creativecommons.org/licenses/by/4.0/. Please cite this article as: Zhao, J.; Lee, J.Y.; Camenzind, D.;Wolcott, M.; Lewis, K.; Gillham, O. Multi-Component Resilience Assessment Framework for a Supply Chain System. Sustainability 2023, 15, 6197. https://doi.org/10.3390/su15076197The goal of this paper is to develop a quantitative resilience assessment framework for a supply chain system exposed to multiple risk factors. Most existing studies on supply chain resilience have primarily focused on assessing the system\u2019s ability to withstand and recover from disruptions caused by a single type of hazard. However, a supply chain system is exposed to multiple exogenous and endogenous events and conditions over a planning horizon, and a comprehensive assessment of resilience should take into account multiple risk factors. Moreover, contrary to the conventional resilience assessment methods focusing on the short duration during which the system is impacted by a disaster event, the proposed framework measures the resilience capacities of the system over a long-term horizon through multi-risk assessment and multi-component resilience assessment. Specifically, a new multi-component resilience index is proposed to measure (a) hazard-induced cumulative loss of functionality, (b) opportunity-induced cumulative gain of functionality, and (c) non-hazard-induced cumulative loss of functionality. The case study results indicate that all three types of risk factors contribute to the overall resilience index significantly and ignoring any one of them may result in inaccurate supply chain performance and resilience assessment

Multi-Component Resilience Assessment Framework for a Supply Chain System

The goal of this paper is to develop a quantitative resilience assessment framework for a supply chain system exposed to multiple risk factors. Most existing studies on supply chain resilience have primarily focused on assessing the system's ability to withstand and recover from disruptions caused by a single type of hazard. However, a supply chain system is exposed to multiple exogenous and endogenous events and conditions over a planning horizon, and a comprehensive assessment of resilience should take into account multiple risk factors. Moreover, contrary to the conventional resilience assessment methods focusing on the short duration during which the system is impacted by a disaster event, the proposed framework measures the resilience capacities of the system over a long-term horizon through multi-risk assessment and multi-component resilience assessment. Specifically, a new multi-component resilience index is proposed to measure (a) hazard-induced cumulative loss of functionality, (b) opportunity-induced cumulative gain of functionality, and (c) non-hazard-induced cumulative loss of functionality. The case study results indicate that all three types of risk factors contribute to the overall resilience index significantly and ignoring any one of them may result in inaccurate supply chain performance and resilience assessment