Canonical babbling trajectories across the first year of life in autism and typical development.

LAY ABSTRACT: Our study examined how babies develop their ability to talk to help identify early signs of autism. We looked at babies' production of babbling with mature syllables across the first year of life. Babies usually start producing mature babbling at 7 months of age before they say their first words. Some studies have suggested that babies who are later diagnosed with autism produce this kind of babbling less frequently in their first year of life, but other studies have shown complicated outcomes. In this new study, we followed 44 autistic babies and compared them to 127 typically developing babies. We recorded the babies once every month, all day long, from the time that they were born until they were around 13 months old. Then, we studied their mature babbling from segments of these recordings. We found that the rate at which babies used mature babbling was lower in boys with autism, and higher in girls with autism, compared to babies without autism. This research helps us understand how babies with autism learn to talk. It also raises important questions about differences between boys and girls with autism. Our study can help us improve how scientists and clinicians can identify autism earlier, which could lead to better communication supports for autistic children and their families.

Foundations of Vocal Category Development in Autistic Infants.

The present study compared the infant's tendency in the first year of life to produce clusters of particular vocal types (squeals, vocants, and growls) in typically developing (TD) and autistic infants. Vocal clustering provides evidence of vocal category formation and may establish a foundation for speech development. Specifically, we compared the extent of vocal clustering across outcome groups and age groups. We also examined the associations between the extent of vocal clustering and later outcomes at 2 years within the autistic group. Randomly selected 5-min segments (27,153 5-min segments total) from 1293 all-day home recordings from 103 TD infants and 44 autistic infants across the first year were humancoded (about 9.75 h of data coded per infant on average) to derive vocal clustering patterns. Fisher's exact tests were used to compare the occurrence of squeals versus vocants, as well as growls versus vocants, across coded segments. Infants in both groups demonstrated clear clustering patterns of squeals and growls across all age groups. The extent of vocal clustering in the autistic group did not correlate significantly with later language, repetitive behavior, or autism severity outcomes. These findings highlight the robustness of the systematic production of vocal categories across the first year of life. The similarity of the clustering patterns in the TD and autistic groups suggests that vocal category formation through active infant vocal exploration is a robust feature of early speech development.

Infant vocal category exploration as a foundation for speech development.

Non-random exploration of infant speech-like vocalizations (e.g., squeals, growls, and vowel- like sounds or "vocants") is pivotal in speech development. This type of vocal exploration, often noticed when infants produce particular vocal types in clusters, serves two crucial purposes: it establishes a foundation for speech because speech requires formation of new vocal categories, and it serves as a basis for vocal signaling of wellness and interaction with caregivers. Despite the significance of clustering, existing research has largely relied on subjective descriptions and anecdotal observations regarding early vocal category formation. In this study, we aim to address this gap by presenting the first large-scale empirical evidence of vocal category exploration and clustering throughout the first year of life. We observed infant vocalizations longitudinally using all-day home recordings from 130 typically developing infants across the entire first year of life. To identify clustering patterns, we conducted Fisher's exact tests to compare the occurrence of squeals versus vocants, as well as growls versus vocants. We found that across the first year, infants demonstrated clear clustering patterns of squeals and growls, indicating that these categories were not randomly produced, but rather, it seemed, infants actively engaged in practice of these specific categories. The findings lend support to the concept of infants as manifesting active vocal exploration and category formation, a key foundation for vocal language.

Vocal Characteristics of Infants at Risk for Speech Motor Involvement: A Scoping Review.

PURPOSE: The purpose of this scoping review was to (a) summarize methodological characteristics of studies examining vocal characteristics of infants at high risk for neurological speech motor involvement and (b) report the state of the high-quality evidence on vocal characteristic trends of infants diagnosed or at high risk for cerebral palsy (CP). METHOD: The PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-Analyses) extension for scoping reviews was followed for reporting our review. Studies measured prelinguistic vocal characteristics of infants under 24 months with birth risk or genetic conditions known to commonly present with speech motor involvement. Fifty-five studies met criteria for Part 1. Eleven studies met criteria for synthesis in Part 2. RESULTS: A smaller percentage of studies examined infants with or at risk for CP compared to studies examining genetic conditions such as Down syndrome. The median year of publication was 1999, with a median sample size of nine participants. Most studies were conducted in laboratory settings and used human coding of vocalizations produced during caregiver-child interactions. Substantial methodological differences were noted across all studies. A small number of high-quality studies of infants with or at risk for CP revealed high rates of marginal babbling, low rates of canonical babbling, and limited consonant diversity under 24 months. Mixed findings were noted across studies of general birth risk factors. CONCLUSIONS: There is limited evidence available to support the early detection of speech motor involvement. Large methodological differences currently impact the ability to synthesize findings across studies. There is a critical need to conduct longitudinal research with larger sample sizes and advanced, modern technologies to detect vocal precursors of speech impairment to support the accurate diagnosis and prognosis of speech development in infants with CP and other clinical populations.

Marginal and Canonical Babbling in 10 Infants at Risk for Cerebral Palsy.

PURPOSE: This study is a preliminary quantification and characterization of the development of marginal and canonical syllable patterns in 10 infants at risk for cerebral palsy (CP). METHOD: We calculated marginal and canonical babbling ratios from parent-infant laboratory recordings of 10 infants at two time points, approximately 13 and 16 months of age. The frequency and diversity of labial, coronal, and velar types of marginal and canonical syllables were also examined. Differences across three outcome groups were compared: infants later diagnosed with CP (n = 3, CP group), risk of CP due to ongoing gross motor delays (n = 4, risk group), and current typically developing status with resolved gross motor delays (n = 3, TDx group). Performance on the Mullen Scales was included for perspective on cognitive development. RESULTS: Higher marginal syllable ratios were observed in the CP and risk groups than the TDx group. An increasing canonical syllable ratio across the two ages was consistently observed in the TDx group. The TDx group produced a greater frequency and diversity of canonical syllable types than the risk and CP groups, and of marginal syllable types than the CP group. CONCLUSIONS: This study offers preliminary support for the possibility that speech motor impairment in infants with CP have the potential to be observed and quantified early in vocal development prior to the expected onset of first words. Prolonged rates of marginal syllable forms may be suggestive of speech motor impairment; however, additional longitudinal outcome data over a longer time course and a larger sample of infants are needed to provide further support for this possibility.

The Effect of Open Access on Scholarly and Societal Metrics of Impact in the ASHA Journals.

PURPOSE: This study examined the effect of open access (OA) status on scholarly and societal metrics of impact (citation counts and altmetric scores, respectively) across manuscripts published in the American Speech-Language-Hearing Association (ASHA) Journals. METHOD: Three thousand four hundred nineteen manuscripts published in four active ASHA Journals were grouped across three access statuses based on their availability to the public: Gold OA, Green OA, and Closed Access. Two linear mixed-effects models tested the effects of OA status on citation counts and altmetric scores of the manuscripts. RESULTS: Both Green OA and Gold OA significantly predicted a 2.70 and 5.21 respective increase in citation counts compared with Closed Access manuscripts (p < .001). Gold OA was estimated to predict a 25.7-point significant increase in altmetric scores (p < .001), but Green OA was only marginally significant (p = .68) in predicting a 1.44 increase in altmetric scores relative to Closed Access manuscripts. DISCUSSION: Communication sciences and disorders (CSD) research that is fully open receives more online attention and, overall, more scientific attention than research that is paywalled or available through Green OA methods. Additional research is needed to understand secondary variables affecting these and other scholarly and societal metrics of impact across studies in CSD. Ongoing support and incentives to reduce the inequities of OA publishing are critical for continued scientific advancement. Open Science Form: https://doi.org/10.23641/asha.21766919.

Open Science Practices in Communication Sciences and Disorders: A Survey.

PURPOSE: Open science is a collection of practices that seek to improve the accessibility, transparency, and replicability of science. Although these practices have garnered interest in related fields, it remains unclear whether open science practices have been adopted in the field of communication sciences and disorders (CSD). This study aimed to survey the knowledge, implementation, and perceived benefits and barriers of open science practices in CSD. METHOD: An online survey was disseminated to researchers in the United States actively engaged in CSD research. Four-core open science practices were examined: preregistration, self-archiving, gold open access, and open data. Data were analyzed using descriptive statistics and regression models. RESULTS: Two hundred twenty-two participants met the inclusion criteria. Most participants were doctoral students (38%) or assistant professors (24%) at R1 institutions (58%). Participants reported low knowledge of preregistration and gold open access. There was, however, a high level of desire to learn more for all practices. Implementation of open science practices was also low, most notably for preregistration, gold open access, and open data (< 25%). Predictors of knowledge and participation, as well as perceived barriers to implementation, are discussed. CONCLUSION: Although participation in open science appears low in the field of CSD, participants expressed a strong desire to learn more in order to engage in these practices in the future. Supplemental Material and Open Science Form: https://doi.org/10.23641/asha.21569040.

A Probe Study on Vocal Development in Two Infants at Risk for Cerebral Palsy.

The present work examined canonical babbling ratios longitudinally as a measure of onset and consolidation of canonical babbling in two infants at risk of cerebral palsy (CP) between 5 and 16 months. Ten typically developing infants were included for comparison at 6, 9, 12, and 16-19 months. Canonical babbling ratios (CBRs) were calculated from 5-min segments, and follow-up diagnostic outcomes were collected between 24 and 33 months. The two infants at risk demonstrated low CBR growth trajectories compared to the typical infant group, and slightly different patterns of consolidation. The two infants at risk were later diagnosed with different levels of CP and speech impairment severity. All infants demonstrated greater variability than expected. Studying canonical babbling and other prelinguistic milestones in this population may inform our perspective of the involvement of the motor system in the vocal domain. Additional implications on the analysis of canonical babbling using all-day home recordings are discussed.

Perspectives on the origin of language: Infants vocalize most during independent vocal play but produce their most speech-like vocalizations during turn taking.

A growing body of research emphasizes both endogenous and social motivations in human vocal development. Our own efforts seek to establish an evolutionary and developmental perspective on the existence and usage of speech-like vocalizations ("protophones") in the first year of life. We evaluated the relative occurrence of protophones in 40 typically developing infants across the second-half year based on longitudinal all-day recordings. Infants showed strong endogenous motivation to vocalize, producing vastly more protophones during independent vocal exploration and play than during vocal turn taking. Both periods of vocal play and periods of turn-taking corresponded to elevated levels of the most advanced protophones (canonical babbling) relative to periods without vocal play or without turn-taking. Notably, periods of turn taking showed even more canonical babbling than periods of vocal play. We conclude that endogenous motivation drives infants' tendencies to explore and display a great number of speech-like vocalizations, but that social interaction drives the production of the most speech-like forms. The results inform our previously published proposal that the human infant has been naturally selected to explore protophone production and that the exploratory inclination in our hominin ancestors formed a foundation for language.

Modelling the genetic aetiology of complex disease: human-mouse conservation of noncoding features and disease-associated loci.

Understanding the genetic aetiology of loci associated with a disease is crucial for developing preventative measures and effective treatments. Mouse models are used extensively to understand human pathobiology and mechanistic functions of disease-associated loci. However, the utility of mouse models is limited in part by evolutionary divergence in transcription regulation for pathways of interest. Here, we summarize the alignment of genomic (exonic and multi-cell regulatory) annotations alongside Mendelian and complex disease-associated variant sites between humans and mice. Our results highlight the importance of understanding evolutionary divergence in transcription regulation when interpreting functional studies using mice as models for human disease variants.

Longitudinal change in speech classification between 4 and 10 years in children with cerebral palsy.

AIM: To examine speech impairment severity classification over time in a longitudinal cohort of children with cerebral palsy (CP). METHOD: A total of 101 children (58 males, 43 females) between the ages of 4 and 10 years with CP participated in this longitudinal study. Speech severity was rated using the Viking Speech Scale (VSS), a four-level classification rating scale, at 4, 6, 8, and 10 years (age 4 years: mean = 52 months [3 SD]; age 6 years: mean = 75 months [2 SD]; age 8 years: mean = 100 months [4 SD]; age 10 years: mean = 125 months [5 SD]). We used Bayesian mixed-effects ordinal logistic regression to model (1) the extent to which speech severity changed over time and (2) patterns of change across age groups and classification rating group levels. RESULTS: VSS ratings decreased (speech severity became less severe) between 4 and 10 years of age. Children who were first classified in VSS levels I, II, or III at age 4 years had a high probability of staying at, or improving to, VSS level I by 10 years. Children who were first classified in VSS level IV at 4 years had a high probability of remaining in VSS level IV at 10 years. INTERPRETATION: Early speech performance is highly predictive of later childhood speech abilities. Children with any level of speech impairment at age 4 years should be receiving speech therapy. Those with more severe speech impairments should be introduced to augmentative and alternative communication as soon as possible. WHAT THIS PAPER ADDS: Children with early Viking Speech Scale (VSS) ratings below level IV have a good prognosis for speech improvement. Children with early VSS level IV ratings are likely to remain at VSS level IV over time. Children did not show worsening of VSS level between the ages of 4 and 10 years.

Cambio longitudinal en la clasificación del habla entre los 4 y 10 años en niños con parálisis cerebral OBJETIVO: Examinar la clasificación de la gravedad del deterioro del habla a lo largo del tiempo en una cohorte longitudinal de niños con parálisis cerebral (PC) entre las edades de 4 y 10 años. MÉTODO: Un total de 101 niños (58 varones, 43 mujeres) con PC participaron en este estudio longitudinal. La gravedad del habla se evaluó utilizando la Viking Speech Scale (VSS), una escala de calificación de clasificación de cuatro niveles, a los 4, 6, 8 y 10 años (edad 4 años: media = 52 meses [3 DE]; edad 6 años: media = 75 meses [2 DE]; edad 8 años: media = 100 meses [4 DE]; edad 10 años: media = 125 meses [5 DE]). Utilizamos la regresión logística ordinal de efectos mixtos bayesianos para modelar (1) la medida en que la severidad del habla cambió con el tiempo y (2) los patrones de cambio entre los grupos de edad y los niveles de clasificación de los grupos. RESULTADOS: Las calificaciones de VSS disminuyeron (la severidad del habla se volvió menos severa) entre los 4 y los 10 años de edad. Los niños que fueron clasificados por primera vez en los niveles I, II o III de VSS a los 4 años tenían una alta probabilidad de permanecer en el nivel I de VSS o mejorar al nivel I de VSS a los 10 años. Los niños que fueron clasificados por primera vez en el nivel IV de VSS a los 4 años tenían una alta probabilidad de permanecer en el nivel IV de VSS a los 10 años. INTERPRETACIÓN: El desempeño temprano del habla es altamente predictivo de las habilidades del habla en la niñez posterior. Los niños con cualquier nivel de discapacidad del habla a la edad de 4 años deben recibir terapia del habla. Aquellos con impedimentos del habla más severos deben ser introducidos a la comunicación aumentativa y alternativa tan pronto como sea posible.

Mudança longitudinal na classificação da fala entre 4 e 10 anos em crianças com paralisia cerebral OBJETIVO: Analisar a classificação da gravidade do comprometimento da fala ao longo do tempo em uma coorte longitudinal de crianças com paralisia cerebral (PC) entre 4 e 10 anos. MÉTODO: Um total de 101 crianças (58 meninos, 43 meninas) com PC participaram deste estudo longitudinal. A gravidade da fala foi avaliada usando a Viking Speech Scale (VSS), uma escala de classificação de quatro níveis, aos 4, 6, 8 e 10 anos (idade 4 anos: média = 52 meses [3 DP]; idade 6 anos: média = 75 meses [2 DP]; idade 8 anos: média = 100 meses [4 DP]; idade 10 anos: média = 125 meses [5 DP]). Usamos a regressão logística ordinal Bayesiana de efeitos mistos para modelar (1) a extensão em que a gravidade da fala mudou ao longo do tempo e (2) padrões de mudança entre as faixas etárias e os níveis de classificação do grupo. RESULTADOS: As classificações de VSS diminuíram (a gravidade da fala tornou-se menos grave) entre 4 e 10 anos de idade. As crianças que foram classificadas pela primeira vez nos níveis VSS I, II ou III aos 4 anos de idade tiveram uma alta probabilidade de permanecer ou melhorar para o nível VSS I em 10 anos. As crianças que foram classificadas pela primeira vez em VSS nível IV aos 4 anos tiveram alta probabilidade de permanecer no VSS nível IV aos 10 anos. INTERPRETAÇÃO: O desempenho precoce da fala é altamente preditivo de habilidades de fala na infância posteriormente. Crianças com qualquer nível de deficiência de fala aos 4 anos de idade devem receber terapia da fala. Aqueles com deficiências de fala mais graves devem ser introduzidos à comunicação aumentativa e alternativa o mais rápido possível.

Mouse genomic and cellular annotations.

Mice have emerged as one of the most popular and valuable model organisms in the research of human biology. This is due to their genetic and physiological similarity to humans, short generation times, availability of genetically homologous inbred strains, and relatively easy laboratory maintenance. Therefore, following the release of the initial human reference genome, the generation of the mouse reference genome was prioritised and represented an important scientific resource for the mouse genetics community. In 2002, the Mouse Genome Sequencing Consortium published an initial draft of the mouse reference genome which contained ~ 96% of the euchromatic genome of female C57BL/6 J mice. Almost two decades on from the publication of the initial draft, sequencing efforts have continued to increase the completeness and accuracy of the C57BL/6 J reference genome alongside advances in genome annotation. Additionally new sequencing technologies have provided a wealth of data that has added to the repertoire of annotations associated with traditional genomic annotations. Including but not limited to advances in regulatory elements, the 3D genome and individual cellular states. In this review we focus on the reference genome C57BL/6 J and summarise the different aspects of genomic and cellular annotations, as well as their relevance to mouse genetic research. We denote a genomic annotation as a functional unit of the genome. Cellular annotations are annotations of cell type or state, defined by the transcriptomic expression profile of a cell. Due to the wide-ranging number and diversity of annotations describing the mouse genome, we focus on gene, repeat and regulatory element annotation as well as two relatively new technologies; 3D genome architecture and single-cell sequencing outlining their utility in genetic research and their current challenges.

Making sense of the linear genome, gene function and TADs.

BACKGROUND: Topologically associating domains (TADs) are thought to act as functional units in the genome. TADs co-localise genes and their regulatory elements as well as forming the unit of genome switching between active and inactive compartments. This has led to the speculation that genes which are required for similar processes may fall within the same TADs, allowing them to share regulatory programs and efficiently switch between chromatin compartments. However, evidence to link genes within TADs to the same regulatory program is limited. RESULTS: We investigated the functional similarity of genes which fall within the same TAD. To do this we developed a TAD randomisation algorithm to generate sets of "random TADs" to act as null distributions. We found that while pairs of paralogous genes are enriched in TADs overall, they are largely depleted in TADs with CCCTC-binding factor (CTCF) ChIP-seq peaks at both boundaries. By assessing gene constraint as a proxy for functional importance we found that genes which singly occupy a TAD have greater functional importance than genes which share a TAD, and these genes are enriched for developmental processes. We found little evidence that pairs of genes in CTCF bound TADs are more likely to be co-expressed or share functional annotations than can be explained by their linear proximity alone. CONCLUSIONS: These results suggest that algorithmically defined TADs consist of two functionally different groups, those which are bound by CTCF and those which are not. We detected no association between genes sharing the same CTCF TADs and increased co-expression or functional similarity, other than that explained by linear genome proximity. We do, however, find that functionally important genes are more likely to fall within a TAD on their own suggesting that TADs play an important role in the insulation of these genes.

Functional Communication Abilities in Youth With Cerebral Palsy: Association With Impairment Profiles and School-Based Therapy Goals.

PURPOSE: The aim of this study was to examine the relationship between functional communication skills, underlying speech, language, and cognitive impairments and school-based speech pathology services in students with cerebral palsy (CP). METHOD: Thirty-five participants with CP who had Individualized Education Programs (IEPs) were classified according to the Communication Function Classification System (CFCS). Participants completed laboratory assessments of speech, receptive language, executive functioning, and nonverbal cognition. Each participant's speech and language IEP goals were coded into treatment units and then categorized into seven, mutually exclusive target goal areas. Nonparametric analyses were employed to examine differences among CFCS groups in the number of deficit areas and the number of goal areas from the IEP. Descriptive analyses were used to evaluate the extent to which deficit and goal areas in the IEP co-occurred by CFCS level. RESULTS: Those in more involved CFCS levels demonstrated more severe speech, receptive language, and cognitive impairments. However, there were no significant differences in the number of deficit areas across CFCS groups. Regardless of CFCS level, there were no differences in the number of treatment goals specified in the IEP. Literacy was the only goal area addressed across all CFCS levels. Those in the most involved CFCS levels had augmentative and alternative communication (AAC) goals, but those with more moderate restrictions in functional communication who also had markedly reduced speech intelligibility did not typically have speech or AAC goals. INTERPRETATION: Individuals with CP across CFCS levels demonstrate variability in underlying deficit profiles, suggesting that measures of both functional communication and of underlying deficits are necessary to provide a complete picture of communication needs. Literacy goals were common across all CFCS levels, but AAC goals were limited to the most severely involved individuals, suggesting that continuing education may be necessary to support speech-language pathologists in developing treatments involving the integration of AAC and speech to foster functional communication at school. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.16968073.

The origin of language and relative roles of voice and gesture in early communication development.

Both vocalization and gesture are universal modes of communication and fundamental features of language development. The gestural origins theory proposes that language evolved out of early gestural use. However, evidence reported here suggests vocalization is much more prominent in early human communication than gesture is. To our knowledge no prior research has investigated the rates of emergence of both gesture and vocalization across the first year in human infants. We evaluated the rates of gestures and speech-like vocalizations (protophones) in 10 infants at 4, 7, and 11 months of age using parent-infant laboratory recordings. We found that infant protophones outnumbered gestures substantially at all three ages, ranging from >35 times more protophones than gestures at 3 months, to >2.5 times more protophones than gestures at 11 months. The results suggest vocalization, not gesture, is the predominant mode of communication in human infants in the first year.

Early Vocal Development in Tuberous Sclerosis Complex.

BACKGROUND: Our goal was to assess for the first time early vocalizations as precursors to speech in audio-video recordings of infants with tuberous sclerosis complex (TSC). METHODS: We randomly selected 40 infants with TSC from the TSC Autism Center of Excellence Research Network dataset. Using human observers, we analyzed 74 audio-video recordings within a flexible software-based coding environment. During the recordings, infants were engaged in developmental testing. We determined syllables per minute (volubility), the number of consonant-vowel combinations, such as 'ba' (canonical babbling), and the canonical babbling ratio (canonical syllables/total syllables) and compared the data with two groups of typically developing (TD) infants. One comparison group's data had come from a laboratory setting, while the other's had come from all-day Language Environment Analysis recordings at home. RESULTS: Compared with TD infants in laboratory and all-day Language Environment Analysis recordings, entry into the canonical babbling stage was delayed in the majority of infants with TSC, and the canonical babbling ratio was low (TD mean = 0.346, SE = 0.19; TSC mean = 0.117, SE = 0.023). Volubility level in infants with TSC was less than half that of TD infants (TD mean = 9.82, SE = 5.78; TSC mean = 3.99, SE = 2.16). CONCLUSIONS: Entry into the canonical stage and other precursors of speech development were delayed in infants with TSC and may signal poor language and developmental outcomes. Future studies are planned to assess prediction of language and developmental outcomes using these measures in a larger sample and in more precisely comparable recording circumstances.

Protophones, the precursors to speech, dominate the human infant vocal landscape.

Human infant vocalization is viewed as a critical foundation for vocal learning and language. All apes share distress sounds (shrieks and cries) and laughter. Another vocal type, speech-like sounds, common in human infants, is rare but not absent in other apes. These three vocal types form a basis for especially informative cross-species comparisons. To make such comparisons possible we need empirical research documenting the frequency of occurrence of all three. The present work provides a comprehensive portrayal of these three vocal types in the human infant from longitudinal research in various circumstances of recording. Recently, the predominant vocalizations of the human infant have been shown to be speech-like sounds, or 'protophones', including both canonical and non-canonical babbling. The research shows that protophones outnumber cries by a factor of at least five based on data from random-sampling of all-day recordings across the first year. The present work expands on the prior reports, showing the protophones vastly outnumber both cry and laughter in both all-day and laboratory recordings in various circumstances. The data provide new evidence of the predominance of protophones in the infant vocal landscape and illuminate their role in human vocal learning and the origin of language. This article is part of the theme issue 'Vocal learning in animals and humans'.

Linking the FTO obesity rs1421085 variant circuitry to cellular, metabolic, and organismal phenotypes in vivo.

Variants in FTO have the strongest association with obesity; however, it is still unclear how those noncoding variants mechanistically affect whole-body physiology. We engineered a deletion of the rs1421085 conserved cis-regulatory module (CRM) in mice and confirmed in vivo that the CRM modulates Irx3 and Irx5 gene expression and mitochondrial function in adipocytes. The CRM affects molecular and cellular phenotypes in an adipose depot-dependent manner and affects organismal phenotypes that are relevant for obesity, including decreased high-fat diet-induced weight gain, decreased whole-body fat mass, and decreased skin fat thickness. Last, we connected the CRM to a genetically determined effect on steroid patterns in males that was dependent on nutritional challenge and conserved across mice and humans. Together, our data establish cross-species conservation of the rs1421085 regulatory circuitry at the molecular, cellular, metabolic, and organismal level, revealing previously unknown contextual dependence of the variant's action.

Social and endogenous infant vocalizations.

Research on infant vocal development has provided notable insights into vocal interaction with caregivers, elucidating growth in foundations for language through parental elicitation and reaction to vocalizations. A role for infant vocalizations produced endogenously, potentially providing raw material for interaction and a basis for growth in the vocal capacity itself, has received less attention. We report that in laboratory recordings of infants and their parents, the bulk of infant speech-like vocalizations, or "protophones", were directed toward no one and instead appeared to be generated endogenously, mostly in exploration of vocal abilities. The tendency to predominantly produce protophones without directing them to others occurred both during periods when parents were instructed to interact with their infants and during periods when parents were occupied with an interviewer, with the infants in the room. The results emphasize the infant as an agent in vocal learning, even when not interacting socially and suggest an enhanced perspective on foundations for vocal language.