New frontiers in translational research: Touchscreens,open science,and the mouse translational research accelerator platform

Many neurodegenerative and neuropsychiatric diseases and other brain disorders are accompanied by impairments in high-level cognitive functions including memory, attention, motivation, and decision-making. Despite several decades of extensive research, neuroscience is little closer to discovering new treatments. Key impediments include the absence of validated and robust cognitive assessment tools for facilitating translation from animal models to humans. In this review, we describe a state-of-the-art platform poised to overcome these impediments and improve the success of translational research, the Mouse Translational Research Accelerator Platform (MouseTRAP), which is centered on the touchscreen cognitive testing system for rodents. It integrates touchscreen-based tests of high-level cognitive assessment with state-of-the art neurotechnology to record and manipulate molecular and circuit level activity in vivo in animal models during human-relevant cognitive performance. The platform also is integrated with two Open Science platforms designed to facilitate knowledge and data-sharing practices within the rodent touchscreen community, touchscreencognition.org and mousebytes.ca. Touchscreencognition.org includes the Wall, showcasing touchscreen news and publications, the Forum, for community discussion, and Training, which includes courses, videos, SOPs, and symposia. To get started, interested researchers simply create user accounts. We describe the origins of the touchscreen testing system, the novel lines of research it has facilitated, and its increasingly widespread use in translational research, which is attributable in part to knowledge-sharing efforts over the past decade. We then identify the unique features of MouseTRAP that stand to potentially revolutionize translational research, and describe new initiatives to partner with similar platforms such as McGill's M3 platform (m3platform.org).     

Absence of heartbeat in the Xenopus tropicalis mutation muzak is caused by a nonsense mutation in cardiac myosin myh6

Mechanisms coupling heart function and cardiac morphogenesis can be accessed in lower vertebrate embryos that can survive to swimming tadpole stages on diffused oxygen. Forward genetic screens in Xenopus tropicalis have identified more than 80 mutations affecting diverse developmental processes, including cardiac morphogenesis and function. In the first positional cloning of a mutation in X. tropicalis, we show that non-contractile hearts in muzak (muz) embryos are caused by a premature stop codon in the cardiac myosin heavy chain gene myh6. The mutation deletes the coiled-coil domain responsible for polymerization into thick filaments, severely disrupting the cardiomyocyte cytoskeleton. Despite the lack of contractile activity and absence of a major structural protein, early stages of cardiac morphogenesis including looping and chamber formation are grossly normal. Muz hearts subsequently develop dilated chambers with compressed endocardium and fail to form identifiable cardiac valves and trabeculae.     

Incorporating microglia-like cells in human induced pluripotent stem cell-derived retinal organoids

Microglia are the primary resident immune cells in the retina. They regulate neuronal survival and synaptic pruning making them essential for normal development. Following injury, they mediate adaptive responses and under pathological conditions they can trigger neurodegeneration exacerbating the effect of a disease. Retinal organoids derived from human induced pluripotent stem cells (hiPSCs) are increasingly being used for a range of applications, including disease modelling, development of new therapies and in the study of retinogenesis. Despite many similarities to the retinas developed in vivo, they lack some key physiological features, including immune cells. We engineered an hiPSC co-culture system containing retinal organoids and microglia-like (iMG) cells and tested their retinal invasion capacity and function. We incorporated iMG into retinal organoids at 13 weeks and tested their effect on function and development at 15 and 22 weeks of differentiation. Our key findings showed that iMG cells were able to respond to endotoxin challenge in monocultures and when co-cultured with the organoids. We show that retinal organoids developed normally and retained their ability to generate spiking activity in response to light. Thus, this new co-culture immunocompetent in vitro retinal model provides a platform with greater relevance to the in vivo human retina.     

Kuru and Cannibalism?

Kuru: Early Letters and Field-Notes from the Collection of D. Carleton Gajdusek . Judith Farquhar and D. Carleton Gajdusek , eds.     

Multiple reputation domains and cooperative behaviour in two Latin American communities

Reputations are a ubiquitous feature of human social life, and a large literature has been dedicated to explaining the relationship between prosocial reputations and cooperation in social dilemmas. However, humans form reputations in domains other than prosociality, such as economic competency that could affect cooperation. To date, no research has evaluated the relative effects of multiple reputation domains on cooperation. To bridge this gap, we analyse how prosocial and competency reputations affect cooperation in two Latin American communities (Bwa Mawego, Dominica, and Pucucanchita, Peru) across a number of social contexts (Dominica: labour contracting, labour exchange and conjugal partnership formation; Peru: agricultural and health advice network size). First, we examine the behavioural correlates of prosocial and competency reputations. Following, we analyse whether prosocial, competency, or both reputation domains explain the flow of cooperative benefits within the two communities. Our analyses suggest that (i) although some behaviours affect both reputation domains simultaneously, each reputation domain has a unique behavioural signature; and (ii) competency reputations affect cooperation across a greater number of social contexts compared to prosocial reputations. Results are contextualized with reference to the social markets in which behaviour is embedded and a call for greater theory development is stressed.