High-Throughput Functional Analysis of CFTR and Other Apically Localized Proteins in iPSC-Derived Human Intestinal Organoids

Induced Pluripotent Stem Cells (iPSCs) can be differentiated into epithelial organoids that recapitulate the relevant context for CFTR and enable testing of therapies targeting Cystic Fibrosis (CF)-causing mutant proteins. However, to date, CF-iPSC-derived organoids have only been used to study pharmacological modulation of mutant CFTR channel activity and not the activity of other disease-relevant membrane protein constituents. In the current work, we describe a high-throughput, fluorescence-based assay of CFTR channel activity in iPSC-derived intestinal organoids and describe how this method can be adapted to study other apical membrane proteins. Specifically, we show how this assay can be employed to study CFTR and ENaC channels and an electrogenic acid transporter in the same iPSC-derived intestinal tissue. This phenotypic platform promises to expand CF therapy discovery to include strategies that target multiple determinants of epithelial fluid transport.

A cortical circuit for audio-visual predictions

Learned associations between stimuli in different sensory modalities can shape the way we perceive these stimuli. However, it is not well understood how these interactions are mediated or at what level of the processing hierarchy they occur. Here we describe a neural mechanism by which an auditory input can shape visual representations of behaviorally relevant stimuli through direct interactions between auditory and visual cortices in mice. We show that the association of an auditory stimulus with a visual stimulus in a behaviorally relevant context leads to experience-dependent suppression of visual responses in primary visual cortex (V1). Auditory cortex axons carry a mixture of auditory and retinotopically matched visual input to V1, and optogenetic stimulation of these axons selectively suppresses V1 neurons that are responsive to the associated visual stimulus after, but not before, learning. Our results suggest that cross-modal associations can be communicated by long-range cortical connections and that, with learning, these cross-modal connections function to suppress responses to predictable input.

Group conditions for entrepreneurial visions: role confidence, hierarchical congruences, and the imagining of future in entrepreneurial groups

An essential part of entrepreneurial activity is the drafting and narrating of an entrepreneurial vision. This study is premised on the observation that entrepreneurial groups form an interaction arena for the practice of imagining the future and asks how the content of entrepreneurial visions is shaped by the conditions of the group. Taking an entrepreneurship-as-practice lens, which we enrich with sociological theory on the future (Beckert) and small groups (Fine), we engage in an in-depth case study of 12 entrepreneurial groups. We show how the content of entrepreneurial visions is configured by four elements (i.e., fictional expectation for the business or the group; future orientation that is continuing or divergent) and name two group conditions (i.e., role confidence and hierarchical congruence) that direct their configuration. We propose that lacking role confidence can impede thinking about the future of a business and that narrative hierarchies that challenge structural hierarchies can open a window for divergent future orientation. This study contributes to a novel theoretical understanding of where entrepreneurial visions come from by emphasizing politics of expectations within groups and calling to consider group conditions as a relevant context for entrepreneurial visions.

Exploring domestic energy consumption feedback through interactive annotation

We report on a three-week field study in which participants from nine households were asked to annotate their domestic electricity consumption data using a prototype interactive visualisation. Through an analysis of the annotations and semi-structured interviews, our findings suggest that the intervention helped participants to develop a detailed and accurate understanding of their electricity consumption data. Our results suggest that energy data visualisations can be improved by having users actively manipulate and annotate their data, as doing so encourages reflection on how energy is being used, facilitating insights on how consumption can be reduced. One of the key findings from our thematic analysis was that participants went beyond the data in their reflections, talking about generational issues, upbringing, financial matters, socio-economic comparisons, environmental concern, mistrust towards utilities, convenience, comfort and self-reported waste. Reading beyond the data illustrates the importance of social practices in the context of energy feedback, embedding eco-feedback research into the relevant context of sociology and psychology research.

The process of becoming ‘we’ in an intergroup conflict context: How enhancing intergroup moral similarities leads to common-ingroup identity

With four studies (N = 332) set in a post-conflict context of Bosnia and Herzegovina and with members of two different ethnic groups (Bosniaks and Serbs), we have demonstrated how perceptions of intergroup moral similarity can act as an important precursor of common-ingroup identity. Research on common-ingroup identity has mainly focused on consequences and benefits of such inclusive social categorizations. However, very little is yet known about processes and conditions that could facilitate such inclusive social categorizations. In this paper, we report both cross-sectional as well as experimental evidence demonstrating how perceptions of intergroup moral similarity boost common-ingroup identifications in socially relevant context using members of real adversary social groups. Moreover, we show that learning about outgroups’ morality (with one vignette and one longitudinal intervention study) can facilitate such inclusive social categorizations even long-term.

Context value updating and multidimensional neuronal encoding in the retrosplenial cortex

The retrosplenial cortex (RSC) has diverse functional inputs and is engaged by various sensory, spatial, and associative learning tasks. We examine how multiple functional aspects are integrated on the single-cell level in the RSC and how the encoding of task-related parameters changes across learning. Using a visuospatial context discrimination paradigm and two-photon calcium imaging in behaving mice, a large proportion of dysgranular RSC neurons was found to encode multiple task-related dimensions while forming context-value associations across learning. During reversal learning requiring increased cognitive flexibility, we revealed an increased proportion of multidimensional encoding neurons that showed higher decoding accuracy for behaviorally relevant context-value associations. Chemogenetic inactivation of RSC led to decreased behavioral context discrimination during learning phases in which context-value associations were formed, while recall of previously formed associations remained intact. RSC inactivation resulted in a persistent positive behavioral bias in valuing contexts, indicating a role for the RSC in context-value updating.

“Nous alone enters from outside” - Aristotelian embryology and early Christian philosophy

In a work entitled On the Generation of Animals, Aristotle remarks that “intellect (nous) alone enters from outside (thurathen)”. Interpretations of this passage as dualistic dominate the history of ideas and allow for a joining together of Platonic and Aristotelian doctrine on the soul. This, however, pulls against the well-known Aristotelian position that soul and body are intertwined and interdependent. The most influential interpretations thereby misrepresent Aristotle’s view on soul and lack any real engagement with his embryology. This paper seeks to extract the account of intellect (nous) in Aristotelian embryology from this interpretative background and place it within the context of his mature biological thought. A clear account of the actual import of this statement in its relevant context is given before explaining how it has been misunderstood by various interpretative traditions. The paper finishes by touching on how early commentary by Christian writers, freed as it was from the imperative to synthesise Greek philosophy, differed from those that came after. While realising that Aristotle’s position would not aid them in their explanations of the soul’s survival after death, their engagement with Aristotle’s science allowed for other aspects of theology concerning the fittingness of soul to body.

Fostering Holistic Development with a Designed Multisport Intervention in Physical Education: A Class-Randomized Cross-Over Trial

Physical education (PE) is acknowledged as a relevant context for holistic child and youth development promotion. However, interventional research mostly builds on individual theories focused on specific outcome domains. This study presents a multisport enriched PE intervention that capitalizes on the intersection of different theory-based approaches to motor, cognitive and socio-emotional skills development promotion. With a cross-over design, 181 fifth graders, coming from a past class-randomized trial of enriched or traditional PE in their 1st–3rd grade, were stratified (based on their previous PE experience) and class-randomized to multisport enriched PE or control group. They completed pre-post assessments in motor and sport skills, cool (inhibition, working memory) and hot (decision making) executive functions, prosocial (empathy, cooperation) and antisocial (quick-temperedness, disruptiveness) behaviors. Children in the enriched PE group showed advantages in motor and prosocial skills after the intervention, which were linked by a mediation path, and an interactive effect of past and actual PE experience on decision making but no differential effects on other variables. The results suggest that a PE intervention designed with an integrative theory base, although not allowing disentangling the contribution of individual components to its efficacy, may help pursue benefits in motor and non-motor domains relevant to whole-child development.

Trust and Trust-Engineering in Artificial Intelligence Research: Theory and Praxis

In this paper, I will identify two problems of trust in an AI-relevant context: a theoretical problem and a practical one. I will identify and address a number of skeptical challenges to an AI-relevant theory of trust. In addition, I will identify what I shall term the ‘scope challenge’, which I take to hold for any AI-relevant theory (or collection of theories) of trust that purports to be representationally adequate to the multifarious forms of trust and AI. Thereafter, I will suggest how trust-engineering, a position that is intermediate between the modified pure rational-choice account and an account that gives rise to trustworthy AI, might allow us to address the practical problem of trust, before identifying and critically evaluating two candidate trust-engineering approaches.