Building a collaborative Psychological Science: Lessons Learned from ManyBabies 1

The field of infancy research faces a difficult challenge: Some questions require samples that are simply too large for any 1 lab to recruit and test. ManyBabies aims to address this problem by forming large-scale collaborations on key theoretical questions in developmental science, while promoting the uptake of Open Science practices. Here, we look back on the first project completed under the ManyBabies umbrella—ManyBabies 1—which tested the development of infant-directed speech preference. Our goal is to share the lessons learned over the course of the project and to articulate our vision for the role of large-scale collaborations in the field. First, we consider the decisions made in scaling up experimental research for a collaboration involving 100+ researchers and 70+ labs. Next, we discuss successes and challenges over the course of the project, including the following: protocol design and implementation, data analysis, organisational structures and collaborative workflows, securing funding, and encouraging broad participation in the project. Finally, we discuss the benefits we see both in ongoing ManyBabies projects and in future large-scale collaborations in general, with a particular eye toward developing best practices and increasing growth and diversity in infancy research and psychological science in general. Throughout the article, we include first-hand narrative experiences to illustrate the perspectives of researchers playing different roles within the project. Although this project focused on the unique challenges of infant research, many of the insights we gained can be applied to large-scale collaborations across the broader field of psychology

Metabolic assessment of a novel chronic myelogenous leukemic cell line and an imatinib resistant subline by 1H NMR spectroscopy

The goal of this study was to examine metabolic differences between a novel chronic myelogenous leukemic (CML) cell line, MyL, and a sub-clone, MyL-R, which displays enhanced resistance to the targeted Bcr-Abl tyrosine kinase inhibitor imatinib. 1H nuclear magnetic resonance (NMR) spectroscopy was carried out on cell extracts and conditioned media from each cell type. Both principal component analysis (PCA) and specific metabolite identification and quantification were used to examine metabolic differences between the cell types. MyL cells showed enhanced glucose removal from the media compared to MyL-R cells with significant differences in production rates of the glycolytic end-products, lactate and alanine. Interestingly, the total intracellular creatine pool (creatine + phosphocreatine) was significantly elevated in MyL-R compared to MyL cells. We further demonstrated that the MyL-R cells converted the creatine to phosphocreatine using non-invasive monitoring of perfused alginate-encapsulated MyL-R and MyL cells by in vivo 31P NMR spectroscopy and subsequent HPLC analysis of extracts. Our data demonstrated a clear difference in the metabolite profiles of drug-resistant and sensitive cells, with the biggest difference being an elevation of creatine metabolites in the imatinib-resistant MyL-R cells

A novel approach in the treatment of neuroendocrine gastrointestinal tumors: Additive antiproliferative effects of interferon-γ and meta-iodobenzylguanidine

BACKGROUND: Therapeutic options to effectively inhibit growth and spread of neuroendocrine gastrointestinal tumors are still limited. As both meta-iodobenzylguanidine (MIBG) and interferon-γ (IFNγ) cause antineoplastic effects in neuroendocrine gastrointestinal tumor cells, we investigated the antiproliferative effects of the combination of IFNγ and non-radiolabeled MIBG in neuroendocrine gut STC-1 and pancreatic carcinoid BON tumor cells. METHODS AND RESULTS: IFNγ receptors were expressed in both models. IFNγ dose- and time-dependently inhibited the growth of both STC-1 and of BON tumor cells with IC(50)-values of 95 ± 15 U/ml and 135 ± 10 U/ml, respectively. Above 10 U/ml IFNγ induced apoptosis-specific caspase-3 activity in a time-dependent manner in either cell line and caused a dose-dependent arrest in the S-phase of the cell cycle. Furthermore, IFNγ induced cytotoxic effects in NE tumor cells. The NE tumor-targeted drug MIBG is selectively taken up via norepinephrine transporters, thereby specifically inhibiting growth in NE tumor cells. Intriguingly, IFNγ treatment induced an upregulation of norepinephrine transporter expression in neuroendocrine tumors cells, as determined by semi-quantitative RT-PCR. Co-application of sub-IC(50 )concentrations of IFNγ and MIBG led to additive growth inhibitory effects, which were mainly due to increased cytotoxicity and S-phase arrest of the cell cycle. CONCLUSION: Our data show that IFNγ exerts antiproliferative effects on neuroendocrine gastrointestinal tumor cells by inducing cell cycle arrest, apoptosis and cytotoxicity. The combination of IFNγ with the NE tumor-targeted agent MIBG leads to effective growth control at reduced doses of either drug. Thus, the administration of IFNγ alone and more so, in combination with MIBG, is a promising novel approach in the treatment of neuroendocrine gastrointestinal tumors

Quantifying Sources of Variability in Infancy Research Using the Infant-Directed-Speech Preference

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure

The trajectory of counterfactual simulation in development.

© 2021 American Psychological Association Young children often struggle to answer the question “what would have happened?” particularly in cases where the adult-like “correct” answer has the same outcome as the event that actually occurred. Previous work has assumed that children fail because they cannot engage in accurate counterfactual simulations. Children have trouble considering what to change and what to keep fixed when comparing counterfactual alternatives to reality. However, most developmental studies on counterfactual reasoning have relied on binary yes/no responses to counterfactual questions about complex narratives and so have only been able to document when these failures occur but not why and how. Here, we investigate counterfactual reasoning in a domain in which specific counterfactual possibilities are very concrete: simple collision interactions. In Experiment 1, we show that 5- to 10-year-old children (recruited from schools and museums in Connecticut) succeed in making predictions but struggle to answer binary counterfactual questions. In Experiment 2, we use a multiple-choice method to allow children to select a specific counterfactual possibility. We find evidence that 4- to 6-year-old children (recruited online from across the United States) do conduct counterfactual simulations, but the counterfactual possibilities younger children consider differ from adult-like reasoning in systematic ways. Experiment 3 provides further evidence that young children engage in simulation rather than using a simpler visual matching strategy. Together, these experiments show that the developmental changes in counterfactual reasoning are not simply a matter of whether children engage in counterfactual simulation but also how they do so. (PsycInfo Database Record (c) 2021 APA, all rights reserved

STAT1 and STAT3 in tumorigenesis

The transcription factors STAT1 and STAT3 appear to play opposite roles in tumorigenesis. While STAT3 promotes cell survival/proliferation, motility and immune tolerance and is considered as an oncogene, STAT1 mostly triggers anti-proliferative and pro-apoptotic responses while enhancing anti-tumor immunity. Despite being activated downstream of common cytokine and growth factor receptors, their activation is reciprocally regulated and perturbation in their balanced expression or phosphorylation levels may re-direct cytokine/growth factor signals from proliferative to apoptotic, or from inflammatory to anti-inflammatory. Here we review the functional canonical and non-canonical effects of STAT1 and STAT3 activation in tumorigenesis and their potential cross-regulation mechanisms

Causality and continuity close the gaps in event representations

International audienceImagine you see a video of someone pulling back their leg to kick a soccer ball, and then a soccer ball soaring toward a goal. You would likely infer that these scenes are two parts of the same event, and this inference would likely cause you to remember having seen the moment the person kicked the soccer ball, even if that information was never actually presented (Strickland & Keil, 2011, Cognition, 121[3], 409–415). What cues trigger people to "fill in" causal events from incomplete information? Is it due to the experience they have had with soccer balls being kicked toward goals? Is it the visual similarity of the object in both halves of the video? Or is it the mere spatiotemporal continuity of the event? In three experiments, we tested these different potential mechanisms underlying the "filling-in" effect. Experiment 1 showed that filling in occurs equally in familiar and unfamiliar contexts, indicating that familiarity with specific event schemas is unnecessary to trigger false memory. Experiment 2 showed that the visible continuation of a launched object’s trajectory is all that is required to trigger filling in, regardless of other occurrences in the second half of the scene. Finally, Experiment 3 found that, using naturalistic videos, this filling-in effect is more heavily affected if the object’s trajectory is discontinuous in space/time compared with if the object undergoes a noticeable transformation. Together, these findings indicate that the spontaneous formation of causal event representations is driven by object representation systems that prioritize spatiotemporal information over other object features