Conserved Genes Act as Modifiers of Invertebrate SMN Loss of Function Defects

Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species

Designing for trust: A case of value-sensitive design

In this paper, we consider the meaning, roles, and uses of trust in the economic and public domain, focusing on the task of designing systems for trust in information technology. We analyze this task by means of a survey of what trust means in the economic and public domain, using the model proposed by Lewicki and Bunker, and using the emerging paradigm of value-sensitive design. We explore the difficulties developers face when designing information technology for trust and show how our analysis in conjunction with existing engineering design methods provides means to address these difficulties. Our main case concerns a concrete problem in the economic domain, namely the transfer of control from customs agencies to companies. Control of individual items is increasingly untenable and is replaced by control on the level of companies aimed at determining whether companies can be trusted to be in control of their business and to be in compliance with applicable regulations. This transfer sets the task for companies to establish this trust by means of information technology systems. We argue that this trust can be achieved by taking into account philosophical analyses of trust and by including both parties in the trust relationship as clients for whom the information technology systems are to be designed.Values and TechnologyTechnology, Policy and Managemen