Young minds’ quest for regularity: Evidence from the Turkish causative

Children's remarkable ability to generalize beyond the input and the resulting overregularizations/ irregularizations provide a platform for a discussion of whether morphology learning uses analogy-based, rule-based, or statistical learning procedures. The present study, testing 115 children (aged 3 to 10) on an elicited production task, investigated the acquisition of the irregular distribution in the Turkish causative. Results showed that in early acquisition, to pin down the four causative suffixes, children engaged in comparisons between analogous exemplars. Thereafter to tackle the irregularity in two of the suffixes, children entertained competing hypotheses that yielded overregularizations and irregularizations. Overregularizations were instances of abstraction across the input based on type frequency; irregularizations were attempts to default to erroneous micro-generalizations. Negative correlation between errors and verb frequency suggested that recovery from errors was sensitive to token frequency. The overgeneralize-then-recover pattern that emerged in the acquisition of causative supported an integrated account of the roles of analogy, abstraction, and frequency in morphology learning.

Autophagy-Related Chemoprotection against Sorafenib in Human Hepatocarcinoma: Role of FOXO3 Upregulation and Modulation by Regorafenib

Early acquisition of sorafenib resistance is responsible for the dismal prognosis of advanced hepatocarcinoma (HCC). Autophagy, a catabolic process involved in liver homeostasis, has been associated with chemosensitivity modulation. Forkhead box O3 (FOXO3) is a transcription factor linked to HCC pathogenesis whose role on autophagy-related sorafenib resistance remains controversial. Here, we unraveled the linkage between autophagy and sorafenib resistance in HCC, focusing on the implication of FOXO3 and its potential modulation by regorafenib. We worked with two HepG2-derived sorafenib-resistant HCC in vitro models (HepG2S1 and HepG2S3) and checked HCC patient data from the UALCAN database. Resistant cells displayed an enhanced basal autophagic flux compared to HepG2, showing higher autophagolysosome content and autophagy markers levels. Pharmacological inhibition of autophagy boosted HepG2S1 and HepG2S3 apoptosis and subG1 cells, but reduced viability, indicating the cytoprotective role of autophagy. HCC samples displayed higher FOXO3 levels, being associated with shorter survival and autophagic genes expression. Consistently, chemoresistant in vitro models showed significant FOXO3 upregulation. FOXO3 knockdown suppressed autophagy and caused resistant cell death, demonstrating that overactivation of such pro-survival autophagy during sorafenib resistance is FOXO3-dependent; a cytoprotective mechanism that the second-line drug regorafenib successfully abolished. Therefore, targeting FOXO3-mediated autophagy could significantly improve the clinical efficacy of sorafenib.

Modeling the Interaction Between Perception-Based and Production-Based Learning in Children's Early Acquisition of Semantic Knowledge

Children learn the meaning of words and sentences in their native language at an impressive speed and from highly ambiguous input. To account for this learning, previous computational modeling has focused mainly on the study of perception-based mechanisms like cross-situational learning. However, children do not learn only by exposure to the input. As soon as they start to talk, they practice their knowledge in social interactions and they receive feedback from their caregivers. In this work, we propose a model integrating both perception- and production-based learning using artificial neural networks which we train on a large corpus of crowd-sourced images with corresponding descriptions. We found that production-based learning improves performance above and beyond perception-based learning across a wide range of semantic tasks including both word- and sentence-level semantics. In addition, we documented a synergy between these two mechanisms, where their alternation allows the model to converge on more balanced semantic knowledge. The broader impact of this work is to highlight the importance of modeling language learning in the context of social interactions where children are not only understood as passively absorbing the input, but also as actively participating in the construction of their linguistic knowledge.

Hippocampal Interneurons are Required for Trace Eyeblink Conditioning in Mice

While the hippocampus has been implicated in supporting the association among time-separated events, the underlying cellular mechanisms have not been fully clarified. Here, we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning (tEBC) task. We found that the hippocampal interneurons exhibited conditioned stimulus (CS)-evoked sustained activity, which predicted the performance of conditioned eyeblink responses (CRs) in the early acquisition of the tEBC. Consistent with this, greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC. Moreover, optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC. In contrast, suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs. Our findings highlight the role of hippocampal interneurons in the tEBC, and point to a potential cellular mechanism subserving associative learning.

Evaluating the Acquisition of Semantic Knowledge from Cross-situational Learning in Artificial Neural Networks

When learning their native language, children acquire the meanings of words and sentences from highly ambiguous input without much explicit supervision. One possible learning mechanism is cross-situational learning, which has been successfully tested in laboratory experiments with children. Here we use Artificial Neural Networks to test if this mechanism scales up to more natural language and visual scenes using a large dataset of crowd-sourced images with corresponding descriptions. We evaluate learning using a series of tasks inspired by methods commonly used in laboratory studies of language acquisition. We show that the model acquires rich semantic knowledge both at the word- and sentence-level, mirroring the patterns and trajectory of learning in early childhood. Our work highlights the usefulness of low-level co-occurrence statistics across modalities in facilitating the early acquisition of higher-level semantic knowledge.

Early acquisition of threat conditioning in a selectively-bred anxiety-like rat phenotype: regulation by maternal presence and FGF2

Temperament is an innate, stable predisposition towards particular emotional and behavioral responses. In humans, certain temperaments are associated with a heightened risk of developing anxiety later in life. Non-human animals, including rodents, also exhibit innate, stable dispositions; these are referred to as behavioral phenotypes. The interaction between behavioral phenotype and early life adverse events is critical for the development of maladaptive anxiety. Rodent studies of typically developing animals have identified a number of mechanisms that protect against aversive experiences in early life. One such mechanism is an early life quiescence of threat learning, which protects against the effects of stress and facilitates safety and attachment learning. However, little is known about the factors that alleviate the effects of early life aversive events on phenotypes vulnerable to pathological anxiety. Here, we examined threat learning and the stress response in selectively-bred infant rats that show an anxiety-like phenotype relative to typically developing animals. We investigated the potential roles of maternal presence and the anxiolytic neurotrophic factor fibroblast growth factor 2 (FGF2) in regulating threat learning and the stress response in infant anxiety-like phenotype animals. We observed that rats selectively-bred for anxiety-like behaviors could acquire conditioned freezing earlier in life than typically developing animals. FGF2 administration on postnatal day 1 (PND 1) and maternal presence during threat conditioning were both capable of suppressing this early emergence of conditioned freezing. However, neither FGF2 nor maternal presence during threat conditioning were associated with reduced corticosterone levels during threat conditioning. Our results suggest that although an anxiety-like phenotype may be associated with early threat learning, environmental factors (such as maternal presence) and pharmacological intervention (such as modulation of the FGF2 system) may be capable of counteracting that early aversive learning. Interventions in vulnerable infants may thus decrease the impact of aversive events.

The roles of morphology, phonology, and prosody in reading and spelling multisyllabic words

While most English words are multisyllabic, research on literacy acquisition has tended to focus on early acquisition of monosyllabic words. The processes involved in multisyllabic word reading and spelling in middle childhood are likely to differ from those in monosyllabic reading and spelling. The current paper examines the contributions of morphological awareness (MA; awareness of derivational morphemes), prosodic sensitivity (sensitivity to lexical stress), and phonological awareness (PA; awareness of phonemes) for multisyllabic word reading and spelling, after accounting for background variables (age, vocabulary, nonverbal IQ, short-term memory). Seventy 7–10-year-old children completed a battery of tasks. MA and prosodic sensitivity were independent predictors of multisyllabic reading, while MA and PA were independent predictors of multisyllabic spelling. These results contrast with previous research, which instead found that PA plays a more prominent role while prosodic sensitivity appears to demonstrate only an indirect influence. However, those studies largely examined reading of shorter, one to three syllable words. These findings indicate when words are longer and multisyllabic, prosodic sensitivity, PA, and MA have differing direct influences on literacy. MA and prosodic sensitivity relate to word reading, while MA and PA are important for spelling.

Germination, early development, and creativity in the acquisition of the Yucatec Maya deictic system

The Yucatec Maya language has a highly complex deictic system with interesting typological differences that in addition to demonstratives and locative adverbs also includes ostensive evidentials and modal adverbs. Given that deictic words are among the first that children produce, the aim of this study is to identify the early acquisition that Yucatec Mayan children follow to map out each deictic form. Deictic words taken from spontaneous, longitudinal, transversal corpora and Gaskins's (1990) field work annotations were labeled and analyzed. The results show that children begin by uttering protoforms mapped with prototypical functions of locative and modal adverbs, but the functions of both demonstratives and ostensive evidentials are expressed mostly with the same protoform, which is similar to the deictic organizations of other languages. When children become productive, they overextend functions, which demonstrates a reanalysis of the system before acquisition is complete.