While multiplexing samples using DNA barcoding revolutionized the pace of biomedical discovery, multiplexing of live imaging-based applications has been limited by the number of fluorescent proteins ...that can be deconvoluted using common microscopy equipment. To address this limitation, we develop visual barcodes that discriminate the clonal identity of single cells by different fluorescent proteins that are targeted to specific subcellular locations. We demonstrate that deconvolution of these barcodes is highly accurate and robust to many cellular perturbations. We then use visual barcodes to generate 'Signalome' cell-lines by mixing 12 clones of different live reporters into a single population, allowing simultaneous monitoring of the activity in 12 branches of signaling, at clonal resolution, over time. Using the 'Signalome' we identify two distinct clusters of signaling pathways that balance growth and proliferation, emphasizing the importance of growth homeostasis as a central organizing principle in cancer signaling. The ability to multiplex samples in live imaging applications, both in vitro and in vivo may allow better high-content characterization of complex biological systems.
Concept inventories (CI) are validated, research-based, multiple-choice tests, which are widely used to assess the effectiveness of pedagogical practices in bringing about conceptual change. In order ...to be a useful diagnostic tool, a CI must reflect only the student understanding of the conceptual material. The Force Concept Inventory (FCI) is arguably the standard for testing conceptual understanding of Newtonian mechanics. Studies in the United States and United Kingdom have shown the existence of a gender gap in FCI scores and gains between male and female students. This study aimed to examine whether such a gap exists for Canadian students at a mid-sized university. Four-hundred and thirty-four men and 379 women taking first-term introductory physics courses from the past nine years were assessed with the FCI prior to and after receiving instruction. A gender gap in the pre-instruction and post instruction scores was revealed in favour of male students (p < 0.01). There also existed a gender disparity in the learning gains between the two tests, where males had significantly higher gains (p < 0.01), although the effect size was small. Further analysis found that both male and female students who studied in classes that included interactive engagement methods had somewhat higher gains than students in traditional lecture courses, but that the interactive engagement methods did not eliminate the gender gap between male and female students (p < 0.01). Our results sound a cross-disciplinary note of caution for anyone using concept inventories as research or self-assessment tools.
Les inventaires de concepts sont des questionnaires à choix multiples validés basés sur la recherche qui sont largement utilisés pour évaluer l’efficacité de pratiques pédagogiques en instaurant un changement conceptuel. Afin d’être des outils diagnostiques utiles, les inventaires de concepts doivent refléter uniquement la compréhension qu’a l’étudiant de la matière conceptuelle. Le « Force Concept Inventory (FCI) » est sans aucun doute la norme pour tester la compréhension conceptuelle de la mécanique newtonienne. Des études menées aux États-Unis et au Royaume-Uni ont montré l’existence d’un écart hommes-femmes dans les résultats du FCI et ainsi que dans les acquis. Cette étude vise à déterminer si un tel écart existe parmi les étudiants canadiens dans une université de taille moyenne. Un total de 434 hommes et 379 femmes inscrits à un premier cours d’introduction à la physique au fil des neuf dernières années ont été évalués avec le FCI au tout début et à la toute fin de la session. Les résultats ont révélé un écart hommes-femmes dans les résultats des tests, aussi bien ceux effectués avant le cours que ceux après le cours, en faveur des étudiants masculins (p < 0.01). Ils ont également révélé une disparité entre hommes et femmes dans les acquis d’apprentissage entre les deux tests : les hommes avaient atteint des acquis plus élevés (p < 0.01), bien que l’ampleur de l’effet ait été faible. Des analyses complémentaires ont montré que tant les hommes que les femmes qui avaient étudié dans des classes qui comprenaient des méthodes d’engagement interactif avaient obtenu davantage d’acquis que les étudiants qui avaient suivi des cours magistraux traditionnels, mais que les méthodes d’engagement interactif n’avaient pas éliminé l’écart hommes-femmes parmi les étudiants (p < 0.01). Nos résultats présentent une mise en garde à l’intention de ceux qui utilisent les inventaires de concepts en tant qu’outils de recherche ou d’auto-évaluation, quelle que soit leur discipline.
While molecules that promote the growth of animal cells have been identified, it remains unclear how such signals are orchestrated to determine a characteristic target size for different cell types. ...It is increasingly clear that cell size is determined by size checkpoints—mechanisms that restrict the cell cycle progression of cells that are smaller than their target size. Previously, we described a p38 MAPK-dependent cell size checkpoint mechanism whereby p38 is selectively activated and prevents cell cycle progression in cells that are smaller than a given target size. In this study, we show that the specific target size required for inactivation of p38 and transition through the cell cycle is determined by CDK4 activity. Our data suggest a model whereby p38 and CDK4 cooperate analogously to the function of a thermostat: while p38 senses irregularities in size, CDK4 corresponds to the thermostat dial that sets the target size.
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•Homeostatic mechanisms maintain cells at a given target size•p38 MAPK promotes growth of cells that are smaller than the critical target size•CDK4 determines the target size by regulating both the duration and rate of cell growth
Tan et al. study homeostatic mechanisms that maintain animal cells at their appropriate target size. They find that p38 is part of a sensing mechanism that identifies inappropriately sized cells, while CDK4 is analogous to a thermostat dial that sets the target size set point referenced by p38.
In these newly commissioned essays, leading Whitehead scholars ask a range of important questions about Whitehead's first year of philosophy lectures. Also included in this volume is the text of ...Whitehead's first lecture at Harvard, allowing for a clearer understanding of Whitehead's plans and goals for his first philosophy lectures.
Jason Bell and Seshu Iyengar examine Whitehead’s complicated relationship to Kant, of whom he is highly critical in parts of the Harvard lectures, and yet with whom he also shares some common themes, ...including ‘the limits of both empirical and cognitive investigations, and the role of the subject in generating mechanics’. The chapter argues that while Whitehead called himself anti-Kantian, what he actually rejected was neo-Kantian analytic tendencies, and not Kant himself, who never intended to promote an epistemic prison or to promote subjectivism. In the end, Whitehead’s Harvard lectures ‘represent a harsh rejection of anti-scientific “Kantianism”, but a more careful editorial revision of the scientifically minded Kant, with the addition of new discoveries in science to which Kant did not have access.’
The relationship between what we would call philosophy and science is complex: despite the indubitable links between disciplines undertaken through those fields, there is always a discussion of what ...the nature of that investigative relationship is. At times, this discussion aims to explain a vision of one field or the other as somehow independent. A common ‘refutation’ of philosophy offers begrudging respect to it as the progenitor of scientific inquiry, but one that ultimately fails to come to meaningful terms with the knowledge accorded by modern science. This is not a new discussion: indeed, understanding the link between these fields
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