Children balance theories and evidence in exploration, explanation, and learning

We look at the effect of evidence and prior beliefs on exploration, explanation and learning. In Experiment 1, we tested children both with and without differential prior beliefs about balance relationships (Center Theorists, mean: 82 months; Mass Theorists, mean: 89 months; No Theory children, mean: 62 months). Center and Mass Theory children who observed identical evidence explored the block differently depending on their beliefs. When the block was balanced at its geometric center (belief-violating to a Mass Theorist, but belief-consistent to a Center Theorist), Mass Theory children explored the block more, and Center Theory children showed the standard novelty preference; when the block was balanced at the center of mass, the pattern of results reversed. The No Theory children showed a novelty preference regardless of evidence. In Experiments 2 and 3, we follow-up on these findings, showing that both Mass and Center Theorists selectively and differentially appeal to auxiliary variables (e.g., a magnet) to explain evidence only when their beliefs are violated. We also show that children use the data to revise their predictions in the absence of the explanatory auxiliary variable but not in its presence. Taken together, these results suggest that children’s learning is at once conservative and flexible; children integrate evidence, prior beliefs, and competing causal hypotheses in their exploration, explanation, and learning.American Psychological Foundation (Elizabeth Munsterberg Koppitz Fellowship)James S. McDonnell Foundation (Collaborative Interdisciplinary Grant on Causal Reasoning)National Science Foundation (U.S.) (NSF Faculty Early Career Development Award)Templeton Foundation (Award

The Double-edged Sword of Pedagogy: Modeling the Effect of Pedagogical Contexts on Preschoolers’ Exploratory Play

URL to paper from conference siteHow does explicit instruction affect exploratory play and learning? We present a model that captures pedagogical assumptions (adapted from Shafto and Goodman, 2008) and test the model with a novel experiment looking at 4-year-olds’ exploratory play in pedagogical and non-pedagogical contexts. Our findings are consistent with the model predictions: preschool children limit their exploration in pedagogical contexts, spending most of their free play performing only the demonstrated action. By contrast, children explore broadly both at baseline and after an accidental demonstration. Thus pedagogy constrains children’s exploration for better and for worse; children learn the demonstrated causal relationship but are less likely than children in non-pedagogical contexts to discover and learn other causal relationships.American Psychological Foundation (Elizabeth Munsterberg Koppitz Fellowship)Templeton FoundationJames S. McDonnell Foundatio

"The Block Makes It Go": Causal Language Helps Toddlers Integrate Prediction, Action, and Expectations about Contact Relations

Some researchers have suggested that correlation information and information about action are bound in a single representation: “causal knowledge”. If children have only observed correlation information, do they spontaneously try to generate the effect? Do they represent the relationship as potentially causal? We present three action and looking-time studies that suggest that even when toddlers (mean; 24 months) predict that one event will follow another, they neither initiate the first event to try to generate the second (as preschoolers, mean 47 months, do spontaneously), nor do they expect that the predictive relations will involve physical contact. Toddlers succeed at both of these inferences when the events are described using causal language. This suggests that causal language plays a role in helping children recognize the relationship between prediction, action, and contact causality.American Psychological Foundation (Elizabeth Munsterberg Koppitz Fellowship)McDonnell FoundationMassachusetts Institute of Technology (James H. Ferry Fund grant

Mind the Gap: Investigating Toddlers’ Sensitivity to Contact Relations in Predictive Events

Toddlers readily learn predictive relations between events (e.g., that event A predicts event B). However, they intervene on A to try to cause B only in a few contexts: When a dispositional agent initiates the event or when the event is described with causal language. The current studies look at whether toddlers’ failures are due merely to the difficulty of initiating interventions or to more general constraints on the kinds of events they represent as causal. Toddlers saw a block slide towards a base, but an occluder prevented them from seeing whether the block contacted the base; after the block disappeared behind the occluder, a toy connected to the base did or did not activate. We hypothesized that if toddlers construed the events as causal, they would be sensitive to the contact relations between the participants in the predictive event. In Experiment 1, the block either moved spontaneously (no dispositional agent) or emerged already in motion (a dispositional agent was potentially present). Toddlers were sensitive to the contact relations only when a dispositional agent was potentially present. Experiment 2 confirmed that toddlers inferred a hidden agent was present when the block emerged in motion. In Experiment 3, the block moved spontaneously, but the events were described either with non-causal (“here’s my block”) or causal (“the block can make it go”) language. Toddlers were sensitive to the contact relations only when given causal language. These findings suggest that dispositional agency and causal language facilitate toddlers’ ability to represent causal relationships.John Templeton Foundation (#12667)James S. McDonnell Foundation (Causal Learning Collaborative Initiative)National Science Foundation (U.S.) (Career Award (# 0744213

Repression of Mitochondrial Translation, Respiration and a Metabolic Cycle-Regulated Gene, SLF1, by the Yeast Pumilio-Family Protein Puf3p

Synthesis and assembly of the mitochondrial oxidative phosphorylation (OXPHOS) system requires genes located both in the nuclear and mitochondrial genomes, but how gene expression is coordinated between these two compartments is not fully understood. One level of control is through regulated expression mitochondrial ribosomal proteins and other factors required for mitochondrial translation and OXPHOS assembly, which are all products of nuclear genes that are subsequently imported into mitochondria. Interestingly, this cadre of genes in budding yeast has in common a 3′-UTR element that is bound by the Pumilio family protein, Puf3p, and is coordinately regulated under many conditions, including during the yeast metabolic cycle. Multiple functions have been assigned to Puf3p, including promoting mRNA degradation, localizing nucleus-encoded mitochondrial transcripts to the outer mitochondrial membrane, and facilitating mitochondria-cytoskeletal interactions and motility. Here we show that Puf3p has a general repressive effect on mitochondrial OXPHOS abundance, translation, and respiration that does not involve changes in overall mitochondrial biogenesis and largely independent of TORC1-mitochondrial signaling. We also identified the cytoplasmic translation factor Slf1p as yeast metabolic cycle-regulated gene that is repressed by Puf3p at the post-transcriptional level and promotes respiration and extension of yeast chronological life span when over-expressed. Altogether, these results should facilitate future studies on which of the many functions of Puf3p is most relevant for regulating mitochondrial gene expression and the role of nuclear-mitochondrial communication in aging and longevity

Ancient mtDNA Genetic Variants Modulate mtDNA Transcription and Replication

Although the functional consequences of mitochondrial DNA (mtDNA) genetic backgrounds (haplotypes, haplogroups) have been demonstrated by both disease association studies and cell culture experiments, it is not clear which of the mutations within the haplogroup carry functional implications and which are “evolutionary silent hitchhikers”. We set forth to study the functionality of haplogroup-defining mutations within the mtDNA transcription/replication regulatory region by in vitro transcription, hypothesizing that haplogroup-defining mutations occurring within regulatory motifs of mtDNA could affect these processes. We thus screened >2500 complete human mtDNAs representing all major populations worldwide for natural variation in experimentally established protein binding sites and regulatory regions comprising a total of 241 bp in each mtDNA. Our screen revealed 77/241 sites showing point mutations that could be divided into non-fixed (57/77, 74%) and haplogroup/sub-haplogroup-defining changes (i.e., population fixed changes, 20/77, 26%). The variant defining Caucasian haplogroup J (C295T) increased the binding of TFAM (Electro Mobility Shift Assay) and the capacity of in vitro L-strand transcription, especially of a shorter transcript that maps immediately upstream of conserved sequence block 1 (CSB1), a region associated with RNA priming of mtDNA replication. Consistent with this finding, cybrids (i.e., cells sharing the same nuclear genetic background but differing in their mtDNA backgrounds) harboring haplogroup J mtDNA had a >2 fold increase in mtDNA copy number, as compared to cybrids containing haplogroup H, with no apparent differences in steady state levels of mtDNA-encoded transcripts. Hence, a haplogroup J regulatory region mutation affects mtDNA replication or stability, which may partially account for the phenotypic impact of this haplogroup. Our analysis thus demonstrates, for the first time, the functional impact of particular mtDNA haplogroup-defining control region mutations, paving the path towards assessing the functionality of both fixed and un-fixed genetic variants in the mitochondrial genome

Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA

Mitochondrial transcription factor A (mtTFA/TFAM) is a nucleus-encoded, high-mobility-group-box (HMG-box) protein that regulates transcription of the mitochondrial genome by specifically recognizing light-strand and heavy-strand promoters (LSP, HSP1). TFAM also binds mitochondrial DNA in a non-sequence specific (NSS) fashion and facilitates its packaging into nucleoid structures. However, the requirement and contribution of DNA-bending for these two different binding modes has not been addressed in detail, which prompted this comparison of binding and bending properties of TFAM on promoter and non-promoter DNA. Promoter DNA increased the stability of TFAM to a greater degree than non-promoter DNA. However, the thermodynamic properties of DNA binding for TFAM with promoter and non-specific (NS) DNA were similar to each other and to other NSS HMG-box proteins. Fluorescence resonance energy transfer assays showed that TFAM bends promoter DNA to a greater degree than NS DNA. In contrast, TFAM lacking the C-terminal tail distorted both promoter and non-promoter DNA to a significantly reduced degree, corresponding with markedly decreased transcriptional activation capacity at LSP and HSP1 in vitro. Thus, the enhanced bending of promoter DNA imparted by the C-terminal tail is a critical component of the ability of TFAM to activate promoter-specific initiation by the core mitochondrial transcription machinery

Just do it? Investigating the gap between prediction and action in toddlers' causal inferences

Adults’ causal representations integrate information about predictive relations and the possibility of effective intervention; if one event reliably predicts another, adults can represent the possibility that acting to bring about the first event might generate the second. Here we show that although toddlers (mean age: 24 months) readily learn predictive relationships between physically connected events, they do not spontaneously initiate one event to try to generate the second (although older children, mean age: 47 months, do; Experiments 1 and 2). Toddlers succeed only when the events are initiated by a dispositional agent (Experiment 3), when the events involve direct contact between objects (Experiment 4), or when the events are described using causal language (Experiment 5). This suggests that causal language may help children extend their initial causal representations beyond agent-initiated and direct contact events.James S. McDonnell Foundation (Causal Learning Collaborative)American Psychological FoundationTempleton Foundatio

Structural analysis and DNA binding of the HMG domains of the human mitochondrial transcription factor A

The mitochondrial transcription factor A (mtTFA) is central to assembly and initiation of the mitochondrial transcription complex. Human mtTFA (h-mtTFA) is a dual high mobility group box (HMGB) protein that binds site-specifically to the mitochondrial genome and demarcates the promoters for recruitment of h-mtTFB1, h-mtTFB2 and the mitochondrial RNA polymerase. The stoichiometry of h-mtTFA was found to be a monomer in the absence of DNA, whereas it formed a dimer in the complex with the light strand promoter (LSP) DNA. Each of the HMG boxes and the C-terminal tail were evaluated for their ability to bind to the LSP DNA. Removal of the C-terminal tail only slightly decreased nonsequence specific DNA binding, and box A, but not box B, was capable of binding to the LSP DNA. The X-ray crystal structure of h-mtTFA box B, at 1.35 Å resolution, revealed the features of a noncanonical HMG box. Interactions of box B with other regions of h-mtTFA were observed. Together, these results provide an explanation for the unusual DNA-binding properties of box B and suggest possible roles for this domain in transcription complex assembly

Inhibitory control, but not prolonged object-related experience appears to affect physical problem-solving performance of pet dogs

Human infants develop an understanding of their physical environment through playful interactions with objects. Similar processes may influence also the performance of non-human animals in physical problem-solving tasks, but to date there is little empirical data to evaluate this hypothesis. In addition or alternatively to prior experiences, inhibitory control has been suggested as a factor underlying the considerable individual differences in performance reported for many species. Here we report a study in which we manipulated the extent of object-related experience for a cohort of dogs (Canis familiaris) of the breed Border Collie over a period of 18 months, and assessed their level of inhibitory control, prior to testing them in a series of four physical problem-solving tasks. We found no evidence that differences in object-related experience explain variability in performance in these tasks. It thus appears that dogs do not transfer knowledge about physical rules from one physical problem-solving task to another, but rather approach each task as a novel problem. Our results, however, suggest that individual performance in these tasks is influenced in a complex way by the subject’s level of inhibitory control. Depending on the task, inhibitory control had a positive or a negative effect on performance and different aspects of inhibitory control turned out to be the best predictors of individual performance in the different tasks. Therefore, studying the interplay between inhibitory control and problem-solving performance will make an important contribution to our understanding of individual and species differences in physical problem-solving performance