Limb proportions show developmental plasticity in response to embryo movement

Animals have evolved limb proportions adapted to different environments, but it is not yet clear to what extent these proportions are directly influenced by the environment during prenatal development. The developing skeleton experiences mechanical loading resulting from embryo movement. We tested the hypothesis that environmentally-induced changes in prenatal movement influence embryonic limb growth to alter proportions. We show that incubation temperature influences motility and limb bone growth in West African Dwarf crocodiles, producing altered limb proportions which may, influence post-hatching performance. Pharmacological immobilisation of embryonic chickens revealed that altered motility, independent of temperature, may underpin this growth regulation. Use of the chick also allowed us to merge histological, immunochemical and cell proliferation labelling studies to evaluate changes in growth plate organisation, and unbiased array profiling to identify specific cellular and transcriptional targets of embryo movement. This disclosed that movement alters limb proportions and regulates chondrocyte proliferation in only specific growth plates. This selective targeting is related to intrinsic mTOR (mechanistic target of rapamycin) pathway activity in individual growth plates. Our findings provide new insights into how environmental factors can be integrated to influence cellular activity in growing bones and ultimately gross limb morphology, to generate phenotypic variation during prenatal development

COVID-19 Deliveries: Maternal Features and Neonatal Outcomes

Integrated, data-driven criteria are necessary to evaluate delivery outcomes in pregnancies affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the ongoing COVID-19 pandemic. This study analyzed maternal demographics, clinical characteristics, treatments, and delivery outcomes of 85 ethnically diverse, adult pregnant women who tested positive for SARS-CoV-2 at the time of delivery. Median maternal and gestational ages were 27 years (interquartile range [IQR]: 23–31) and 39 weeks (IQR: 37.3–40.0), respectively. Of the 85 SARS-CoV-2–positive participants, 67 (79%) had no COVID-19 symptoms at the time of routine COVID-19 admission testing, 14 (16%) reported mild COVID-19 symptoms, and 4 (5%) presented severe COVID-19 symptoms that required hospitalization. Patients in the severe COVID-19 group had significantly longer hospitalizations than those with nonsevere COVID-19 (7 [IQR: 4.5–9.5] vs 2 [IQR: 2–3] days; P \u3c 0.01). Neonatal outcomes included 100% live births with a median 1-minute Apgar score of 8 and 15% preterm births. No neonatal deaths or vertical transmissions were reported, and all neonatal intensive care unit admissions were related to prematurity. Overall, maternal symptom prevalence and peripartum complication rates were low, suggesting a generally good prognosis for pregnant women with SARS-CoV-2 infections at the time of delivery

Cooperative Cross-Talk between Neuroblastoma Subtypes Confers Resistance to Anaplastic Lymphoma Kinase Inhibition

Neuroblastoma is a pediatric solid tumor that can be stratified into stroma-rich and stroma-poor histological subgroups. The stromal compartment of neuroblastoma is composed mostly of Schwann cells, and they play critical roles in the differentiation, survival, and angiogenic responses of tumor cells. In certain neuroblastoma cell lines, the coexistence of neuroblastic N-type and substrate-adherent S-type is frequently observed. One such cell line, SK-N-SH, harbors a F1174L oncogenic mutation in the anaplastic lymphoma kinase (ALK) gene. Treatment of SK-N-SH with an ALK chemical inhibitor, TAE684, resulted in the outgrowth of S-type cells that expressed the Schwann cell marker, S100α6. Nucleotide sequencing analysis of these TAE684-resistant (TR) sublines revealed the presence of the ALK F1174L mutation, suggesting their tumor origin, although ALK protein was not detected. Consistent with these findings, TR cells displayed approximately 9-fold higher IC50 values than N-type cells. Also, unlike N-type cells, TR cells have readily detectable phosphorylated STAT3 but weaker phosphorylated AKT. Under coculture conditions, TR cells conferred survival to N-type cells against the apoptotic effect of TAE684. Cocultivation also greatly enhanced the overall phosphorylation of STAT3 and its transcriptional activity in N-type cells. Finally, conditioned medium from TR clones enhanced cell viability of N-type cells, and this effect was phosphatidylinositol 3-kinase dependent. Taken together, these results demonstrate the ability of tumor-derived S-type cells in protecting N-type cells against the apoptotic effect of an ALK kinase inhibitor through upregulating prosurvival signaling

Extensions to the Speech Disorders Classification System (SDCS)

This report describes three extensions to a classification system for pediatric speech sound disorders termed the Speech Disorders Classification System (SDCS). Part I describes a classification extension to the SDCS to differentiate motor speech disorders from speech delay and to differentiate among three subtypes of motor speech disorders. Part II describes the Madison Speech Assessment Protocol (MSAP), an approximately two-hour battery of 25 measures that includes 15 speech tests and tasks. Part III describes the Competence, Precision, and Stability Analytics (CPSA) framework, a current set of approximately 90 perceptual- and acoustic-based indices of speech, prosody, and voice used to quantify and classify subtypes of Speech Sound Disorders (SSD). A companion paper, Shriberg, Fourakis, et al. (2010) provides reliability estimates for the perceptual and acoustic data reduction methods used in the SDCS. The agreement estimates in the companion paper support the reliability of SDCS methods and illustrate the complementary roles of perceptual and acoustic methods in diagnostic analyses of SSD of unknown origin. Examples of research using the extensions to the SDCS described in the present report include diagnostic findings for a sample of youth with motor speech disorders associated with galactosemia ( Shriberg, Potter, & Strand, 2010 ) and a test of the hypothesis of apraxia of speech in a group of children with autism spectrum disorders ( Shriberg, Paul, Black, & van Santen, 2010 ). All SDCS methods and reference databases running in the PEPPER (Programs to Examine Phonetic and Phonologic Evaluation Records; [ Shriberg, Allen, McSweeny, & Wilson, 2001 ]) environment will be disseminated without cost when complete

Perceptual and acoustic reliability estimates for the Speech Disorders Classification System (SDCS)

A companion paper describes three extensions to a classification system for paediatric speech sound disorders termed the Speech Disorders Classification System (SDCS). The SDCS uses perceptual and acoustic data reduction methods to obtain information on a speaker's speech, prosody, and voice. The present paper provides reliability estimates for the two perceptual methods (narrow phonetic transcription; prosody-voice coding) and the acoustic analysis methods the SDCS uses to describe and classify a speaker's speech competence, precision, and stability. Speech samples from 10 speakers, five with significant motor speech disorder and five with typical speech, were re-measured to estimate intra-judge and inter-judge agreement for the perceptual and acoustic methods. Each of the speakers completed five speech tasks (total = 50 datasets), ranging in articulatory difficulty for the speakers, with consequences for the difficulty level of data reduction. Point-to-point percentage of agreement findings for the two perceptual methods were as high or higher than reported in literature reviews and from previous studies conducted within the laboratory. Percentage of agreement findings for the acoustics tasks of segmenting phonemes, editing fundamental frequency tracks, and estimating formants ranged from values in the mid 70% to 100%, with most estimates in the mid 80% to mid 90% range. Findings are interpreted as support for the perceptual and acoustic methods used in the SDCS to describe and classify speakers with speech sound disorders