👤 C François

Auditory event-related brain potentials such as the mismatch negativity (MMN) and the frequency-following response (FFR) allow exploring speech sound encoding along the auditory pathway. Here, we collected event-related brain potential (ERP) and FFR neural responses to syllables in healthy full-term newborns (N = 17, mean age = 3 days) and adults (N = 21, mean age = 22.7). Participants were passively exposed to alternating blocks of syllables presented at either fast or slow stimulation rates while we recorded electroencephalography (EEG). Specifically, blocks containing the synthetic /oa/ syllable alternated with "oddball" blocks containing three natural syllables differing in place of articulation (one standard /da/ and two deviants /ba/ and /ga/). At the FFR level, we found that 3-day-old newborns (i) exhibit an already functional encoding of vowel pitch, (ii) show an immature encoding of vowel formant structure, replicating previous observations. At the ERP level, the two deviants elicited clear MMN in the two groups, although with different topographies, suggesting an immature sensitivity to place of articulation in newborns. These results confirm the role of experience-dependent developmental factors that may differentially shape FFR and ERPs of speech sound features. Furthermore, this study highlights the feasibility of assessing the hierarchy of neural speech sound encoding in a short experimental session. Show less

Children with left perinatal arterial ischemic stroke (PAIS) often exhibit language deficits. However, evaluations of learning abilities are scarce. We compared word-referent associative learning and recall performance using a fast-mapping paradigm in a group of 3.5-year-old children with PAIS and in age-matched controls. The task involved a referent selection phase followed by immediate and delayed recall trials of the novel word-object associations. While no between-group differences were observed in the referent selection and immediate recall, children with PAIS showed lower performance in delayed recall of the newly learned associations. These results suggest that word learning difficulties after PAIS may arise due to a memory retention failure rather than to the process of referent selection through disambiguation involved in the fast mapping task. We discuss these findings in relation to the neural bases of infant language acquisition and their implications for clinical practice, particularly in terms of improving lexical acquisition and retention in children with PAIS. Show less

While a growing body of literature exists on initial word-to-meaning mapping and retrieval of fully lexicalized words, our understanding on the consolidation that occurs between these two stages remains limited. The current study investigated the neural correlates of retrieving newly learned word using oscillatory brain dynamics. Participants learned to associate new words with unknown objects and performed overt and covert naming tasks during the first and last days of a five-day training period. Behavioral results showed improved overt naming on Day 5 compared to Day 1. Selecting only words that were successfully produced in the overt naming task, we examined oscillatory activity associated with word retrieval while participants produced new words covertly, both pre- (Day 1) and post (Day 5) learning. The results showed a robust alpha (8-12 Hz) and lower beta (13-25 Hz) power decrease during covert naming after learning. We hypothesize that this alpha-beta power decrease indexes successful word retrieval following consolidation. Show less

Speech and co-speech gestures always go hand in hand. Whether we find the precursors of these co-speech gestures in infants before they master their native language still remains an open question. Except for deictic gestures, there is little agreement on the existence of iconic, non-referential and conventional gestures before children start producing their first words. Here, we bridge this knowledge gap by leveraging an ethological method already established for describing speech independent gestures in nonhuman primates, to analyze the spontaneous gestures produced by infants when interacting with their caregivers. We manually annotated video recordings of infant-caregiver interactions (26 h) from the CHILDES platform, to describe the gesture forms, types and functions in six infants from 12 to 15 months of age. We describe 62 gesture forms in the preverbal repertoire. These were categorized into deictic, iconic, non-referential and conventional gesture types, similar to co-speech gesture types. We also find that the type-function relation of preverbal gestures map similarly to type-meaning relation of co-speech gestures. Taken together, our results illustrate linguistic properties of infant gestures in the absence of speech, suggesting them to be precursors of co-speech gestures. Show less

Little is known about language development after late-to-moderate premature birth, the most significant part of prematurity worldwide. We examined minimal-pair word-learning skills in 18 eighteen-month-old healthy full-term (mean gestational age [GA] at birth = 39.6 weeks; 7 males; 100% Caucasian) and 18 healthy late-to-moderate preterm infants (mean GA at birth 33.7 weeks; 11 males; 100% Caucasian). Data were collected in the local urban area of Barcelona city from May 2015 to August 2016. Toddlers first associated two pseudo-words, forming a minimal pair based on a voice onset time distinction of the initial consonant, with two unfamiliar objects during a habituation phase. A visual choice test assessed their recognition of the two novel word-object associations and some familiar word-object pairs. While full-terms successfully mapped the similar sounding pair of novel words (d = 1.57), preterms could not (d = 0.17). These results suggest that late to moderate preterm birth can hinder basic associative learning mechanisms relying on fine temporal speech features. Show less

Adipogenesis is a complex process controlled by intrinsic and extrinsic factors that regulate preadipocyte proliferation, adipogenic capacity and maturation of metabolic function. Here we show that insulin and IGF-1 receptors are essential for mature adipocyte survival and that deletion of both IR and IGF1R specifically in fat using a tamoxifen inducible-AdipoQ-Cre (Ai-DKO) leads to rapid and severe loss of adipocytes in all depots, associated with a metabolic syndrome characterized by hypertriglyceridemia, hyperglycemia, hyperinsulinemia, fatty liver, and pancreatic beta cell proliferation. In this model, this pathological phenotype reverses over a few weeks, in large part, due to preadipocyte proliferation and adipose tissue regeneration. Incubation of preadipocytes with serum from the Ai-DKO mice in vitro stimulates cell proliferation, and this effect can be mimicked by conditioned media from liver slices of Ai-DKO mice, but not by media of cultured Ai-DKO adipocytes, indicating a hepatic origin of the growth factor. Proteomic analysis of serum reveals apolipoprotein C3 (APOC3), a protein secreted by liver, as one of the most upregulated proteins in the Ai-DKO mice. In vitro, purified and delipidated APOC3 stimulates preadipocyte proliferation, however, knockdown of hepatic APOC3 in vivo in Ai-DKO mice is not sufficient to block adipose regeneration. Thus, lipodystrophy is associated with presence of increased preadipocyte-stimulating growth factors in serum. Our study indicates that APOC3 is one contributing factor to preadipocyte proliferation, however, other still-unidentified circulating growth factors are also likely present in Ai-DKO mice. Identification of these factors may provide a new approach to regulation of adipose mass in health and disease. Show less

The current study evaluated the role of Hey2 transcription factor in radiation-induced endothelial-to-mesenchymal transition (EndoMT) and its impact on radiation-induced tissue damage in mice. Phenotypic modifications of irradiated, Hey2 siRNA- and Hey2 vector plasmid-transfected human umbilical vein endothelial cells (HUVECs) resembling EndoMT were monitored by qPCR, immunocytochemistry and western blots. Subsequently, in mice, a Cre-LoxP strategy for inactivation of Hey2 specifically in the endothelium was used to study the biological consequences. Total body irradiation and radiation proctitis were monitored to investigate the impact of conditional Hey2 deletion on intestinal stem cells and microvascular compartment radiosensitivity, EndoMT and rectal damage severity. We found that EndoMT occurs in irradiated HUVECs with concomitant Hey2 mRNA and protein increase. While Hey2 silencing has no effect on radiation-induced EndoMT in vitro, Hey2 overexpression is sufficient to induce phenotypic conversion of endothelial cells. In mice, the conditional deletion of Hey2 reduces EndoMT frequency and the severity of rectal tissue damage. Our data indicate that the reduction in mucosal damage occurs through decline in stem/clonogenic epithelial cell loss mediated by microvascular protection. EndoMT is involved in radiation proctitis and this study demonstrates that a strategy based on the reduction of EndoMT mitigates intestinal tissue damage. Show less

The Saccharomyces cerevisiae cwh43-2 mutant, originally isolated for its Calcofluor white hypersensitivity, displays several cell wall defects similar to mutants in the PKC1-MPK1 pathway, including a growth defect and increased release of beta-1,6-glucan and beta-glucosylated proteins into the growth medium at increased temperatures. The cloning of CWH43 showed that it corresponds to YCR017c and encodes a protein with 14-16 transmembrane segments containing several putative phosphorylation and glycosylation sites. The N-terminal part of the amino acid sequence of Cwh43p shows 40% similarity with the mammalian FRAG1, a membrane protein that activates the fibroblast growth factor receptor of rat osteosarcoma (FGFR2-ROS) and with protein sequences of four uncharacterized ORFs from Caenorhabditis elegans and one from Drosophila melanogaster. The C-terminus of Cwh43p shows low similarities with a xylose permease of Bacillus megaterium and with putative sugar transporter from D. melanogaster, and has 52% similarity with a protein sequence from a Schizosaccharomyces pombe cDNA. A Cwh43-GFP fusion protein suggested a plasma membrane localization, although localization to the internal structure of the cells could not be excluded, and it concentrates to the bud tip of small budded cells and to the neck of dividing cells. Deletion of CWH43 resulted in cell wall defects less pronounced than those of the cwh43-2 mutant. This allele-specific phenotype appears to be due to a G-R substitution at position 57 in a highly conserved region of the protein. Genetic analysis places CWH43 upstream of the BCK2 branch of the PKC1 signalling pathway, since cwh43 mutations were synthetic lethal with pkc1 deletion, whereas the cwh43 defects could be rescued by overexpression of BCK2 and not by high-copy-number expression of genes encoding downstream proteins of the PKC1 pathway However, unlike BCK2, whose disruption in a cln3 mutant resulted in growth arrest in G(1), no growth defect was observed in a double cwh43 cln3 mutants. Taken together, it is proposed that CWH43 encodes a protein with putative sensor and transporter domains acting in parallel to the main PKC1-dependent cell wall integrity pathway, and that this gene has evolved into two distinct genes in higher eukaryotes. Show less