Molecular, phenotypic, and sample-associated data to describe pluripotent stem cell lines and derivatives

The use of induced pluripotent stem cells (iPSC) derived from independent patients and sources holds considerable promise to improve the understanding of development and disease. However, optimized use of iPSC depends on our ability to develop methods to efficiently qualify cell lines and protocols, monitor genetic stability, and evaluate self-renewal and differentiation potential. To accomplish these goals, 57 stem cell lines from 10 laboratories were differentiated to 7 different states, resulting in 248 analyzed samples. Cell lines were differentiated and characterized at a central laboratory using standardized cell culture methodologies, protocols, and metadata descriptors. Stem cell and derived differentiated lines were characterized using RNA-seq, miRNA-seq, copy number arrays, DNA methylation arrays, flow cytometry, and molecular histology. All materials, including raw data, metadata, analysis and processing code, and methodological and provenance documentation are publicly available for re-use and interactive exploration at https://www.synapse.org/pcbc. The goal is to provide data that can improve our ability to robustly and reproducibly use human pluripotent stem cells to understand development and disease

Autosomal dominant mitochondrial membrane protein-associated neurodegeneration (MPAN)

BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is caused by pathogenic sequence variants in C19orf12. Autosomal recessive inheritance has been demonstrated. We present evidence of autosomal dominant MPAN and propose a mechanism to explain these cases. METHODS: Two large families with apparently dominant MPAN were investigated; additional singleton cases of MPAN were identified. Gene sequencing and multiplex ligation-dependent probe amplification were used to characterize the causative sequence variants in C19orf12. Post-mortem brain from affected subjects was examined. RESULTS: In two multi-generation non-consanguineous families, we identified different nonsense sequence variations in C19orf12 that segregate with the MPAN phenotype. Brain pathology was similar to that of autosomal recessive MPAN. We additionally identified a preponderance of cases with single heterozygous pathogenic sequence variants, including two with de novo changes. CONCLUSIONS: We present three lines of clinical evidence to demonstrate that MPAN can manifest as a result of only one pathogenic C19orf12 sequence variant. We propose that truncated C19orf12 proteins, resulting from nonsense variants in the final exon in our autosomal dominant cohort, impair function of the normal protein produced from the non-mutated allele via a dominant negative mechanism and cause loss of function. These findings impact the clinical diagnostic evaluation and counseling

WikiPathways App for Cytoscape: Making biological pathways amenable to network analysis and visualization

In this paper we present the open-source WikiPathways app for Cytoscape http://apps.cytoscape.org/apps/wikipathways) that can be used to import biological pathways for data visualization and network analysis. an open, collaborative biological pathway database that provides fully pathway diagrams for manual download or through web services. The app allows users to load pathways in two different views: as an ideal for data visualization and as a simple network to perform analysis. An example pathway and dataset are used to demonstrate the functionality of the WikiPathways app and how they can be combined and together with other apps. More than 3000 downloads in the first 12 following its release in August 2013 highlight the importance and app in the network biology field

The limits of water pricing in a developing country metropolis: empirical lessons from an industrial city of Pakistan

This paper seeks to question the effectiveness of water pricing as a means of consumer behavioural change in urban centres of the Global South by analysing the domestic usage for water in a major industrial city of Pakistan. Using survey data of 1100 households from Faisalabad city, we estimate the price and income elasticities of water demand. Instrumental variable methods are applied to overcome the endogeneity issues of water pricing. The findings reflect that price and income elasticities vary across different groups. Price elasticities range from −0.43 to −0.71, and income elasticities vary between 0.01 and 0.12. These findings suggest that pricing policies may have limited scope to drive households’ water consumption patterns. However, these empirics may suggest that policy makers should design an appropriate tariff structure to increase revenues that can be invested to further improve the existing water infrastructure. The study findings also suggest that non-pricing instruments, such as water saving campaigns, may be helpful in driving an efficient use of water in rapidly growing cities in the developing world

Improving Access and Inclusion in Employment for People with Disabilities: Implementation of Workplace Adjustments in ‘Best-Practice’ Organisations

The Centre for Workplace Leadership (CWL), in consultation with the Australian Network on Disability (AND) and with funding from the Hallmark Disability Research Initiative at the University of Melbourne, embarked on research to: disseminate information about best practice in implementing workplace adjustments; make a meaningful contribution to disability rights advocacy in the employment sphere; facilitate meaningful engagement between academic enquiry and business practice; and aid the pursuit of self-determination and full and equal participation in society by people with disabilities. To achieve these aims, we conducted interviews of managers and employees with disabilities in ‘best-practice’ organisations in Australia