Growth and development of trabecular structure in the calcaneus of Japanese macaques (Macaca fuscata) reflects locomotor behavior, life-history, and neuromuscular development.

We aim to broaden the analysis of bone structure by suggesting a new way to incorporate the interactions between behavior, neuromuscular development, and life-history. We examine the associations between these variables and age-related variation in trabecular structure in the calcaneus of Japanese macaques (Macaca fuscata). If skeletal markers linking these variables can be established, our inferences of the biology and behavior of fossil species would be significantly improved. We μCT scanned the calcaneus in a cross-sectional sample of 36 juveniles aged between 0 and 7 years old and 5 adults at the Primate Research Institute, Japan. We calculated whole bone averages of standard trabecular properties and generated whole-bone morphometric maps of bone volume fraction and Youngs modulus. Trabecular structure is increasingly heterogeneous in older individuals. BV/TV decreases during the first month of life and increases afterwards, coinciding with the onset of independent locomotion. At birth, primary Youngs modulus is oriented orthogonal to the ossification center, but after locomotor onset bone structure becomes stiffest in the direction of joint surfaces and muscle attachments. Age-related variation in bone volume fraction is best predicted by an interaction between neuromaturation, body mass, and locomotor independence. Results support the common assumption that trabecular structure dynamically adapts to novel joint loading conditions during ontogeny. The timing of independent locomotion, body size, and neuromuscular development, are all correlated to age-related variation in the trabecular structure of the macaque calcaneus. The causal mechanisms behind the observed patterns cannot be directly inferred from our cross-sectional study. If the model presented in this paper holds up under longitudinal experimental conditions, trabecular structure can be used both to infer behavior from fossil morphology and to serve as a valuable proxy for neuromuscular maturation and life history events like locomotor onset and the achievement of an adult-like gait.

An exon junction complex-independent function of Barentsz in neuromuscular synapse growth

The exon junction complex controls the translation, degradation and localization of spliced mRNAs, and three of its four core subunits also play a role in splicing. Here we show that the fourth subunit, Barentsz, has distinct biological functions within and separate from the exon junction complex in neuromuscular development. Barentsz controls the distribution of mitochondria in larval muscles, a function that also depends on other subunits of the exon junction complex and that is not rescued by a transgene in which residues required for binding to the core subunit eIF4AIII are mutated. In contrast, interactions with the exon junction complex are not required for Barentsz to promote the growth of neuromuscular synapses. We found that the Activin ligand Dawdle shows reduced expression inbarentszmutants and acts downstream of Barentsz to control synapse growth. Bothbarentszanddawdleare required in motor neurons, muscles and glia for normal synapse growth, and exogenous Dawdle can rescue synapse growth in the absence ofbarentsz. These results identify a biological function for Barentsz that is independent of the exon junction complex.

Transmembrane Collagens in Neuromuscular Development and Disorders

Neuromuscular development is a multistep process and involves interactions among various extracellular and transmembrane molecules that facilitate the precise targeting of motor axons to synaptogenic regions of the target muscle. Collagenous proteins with transmembrane domains have recently emerged as molecules that play essential roles in multiple aspects of neuromuscular formation. Membrane-associated collagens with interrupted triple helices (MACITs) are classified as an unconventional subtype of the collagen superfamily and have been implicated in cell adhesion in a variety of tissues, including the neuromuscular system. Collagen XXV, the latest member of the MACITs, plays an essential role in motor axon growth within the developing muscle. In humans, loss-of-function mutations of collagen XXV result in developmental ocular motor disorders. In contrast, collagen XIII contributes to the formation and maintenance of neuromuscular junctions (NMJs), and disruption of its function leads to the congenital myasthenic syndrome. Transmembrane collagens are conserved not only in mammals but also in organisms such as C. elegans, where a single MACIT, COL-99, has been documented to function in motor innervation. Furthermore, in C. elegans, a collagen-like transmembrane protein, UNC-122, is implicated in the structural and functional integrity of the NMJ. This review article summarizes recent advances in understanding the roles of transmembrane collagens and underlying molecular mechanisms in multiple aspects of neuromuscular development and disorders.

Establishing a Foundation

Chapter Four explores how early childhood music and movement classes might utilize appropriate yoga postures and breath work for very young children from the ages of three to six, concluding with a sample curriculum for an eight-week summer music course. Building on research on the benefits of music education starting in early childhood, as well as research on the importance of slow, integrated movement for optimal learning and neuromuscular development, this chapter shows how introductory musical concepts may be blended with yoga postures and breath work to enhance attention, motivation, and aural awareness. Some of the proposed poses emphasize crossing the midline, which enhances integration across the two hemispheres of the brain. The postures and breath work may also be used with elementary-age students, so the final section describes how specific techniques might be incorporated in the private lesson, as well.

Reflex Epilepsy with Hot Water: Clinical and EEG Findings, Treatment, and Prognosis in Childhood

Hot water epilepsy (HWE) is a subtype of reflex epilepsy in which seizures are triggered by the head being immersed in hot water. Hot water or bathing epilepsy is the type of reflex epilepsy most frequently encountered in our clinic. We describe our patients with HWE and also discuss the clinical features, therapeutic approaches, and prognosis. Eleven patients (10 boys, 1 girl), aged 12 months to 13 years, admitted to the pediatric neurology clinic between January 2018 and August 2019, and diagnosed with HWE or bathing epilepsy based on International League Against Epilepsy (ILAE)-2017, were followed up prospectively for ∼18 months. Patients' clinical and electroencephalography (EEG) findings and treatment details were noted. All 11 patients' seizures were triggered by hot water. Age at first seizure was between 2 months and 12 years. Seizure types were generalized motor seizures, absence, and atonic. EEG was normal in two patients, but nine patients had epileptiform discharges. Magnetic resonance imaging of the brain was performed and reported as normal (except in one case). Histories of prematurity were present in two patients, unprovoked seizures in one, and low birth weight and depressed birth in the other. Patients with HWE have normal neuromuscular development and neurological examination results, together with prophylaxis or seizure control with a single antiepileptic drug, suggesting that it is a self-limited reflex epilepsy.

Neuromuscular Development in Neonates and Postnatal Infants: Implications for Neuromuscular Electrical Stimulation Therapy for Dysphagia

Purpose The aim of the current study was to review neuromuscular development, summarize the current body of evidence describing the use of neuromuscular electrical stimulation (NMES) therapy in infants, and identify possible contraindications for the use of NMES in the neonate and young infant. Method After a review of the literature describing neuromuscular development, we created a timeline of the developmental processes. Key milestones were determined, and a literature search was conducted to identify potential effects of electrical stimulation on this process. Results Current evidence supporting the use of NMES in the pediatric population is limited and of poor quality. Contraindications of the use of NMES in the neonate and young infant were identified, including (a) inhibited expression of the neural cell adhesion molecule that is vital for neuromuscular development, (b) alteration of muscle fiber type metabolic profile away from intended muscle fiber type morphology, and (c) interruption of postsynaptic acetylcholine receptor synthesis during neuromuscular junction development. Conclusion The use of NMES for the treatment of dysphagia in the neonate and young infant may influence early neuromuscular development in a manner that is not currently well understood. Future research is needed to further understand the effects of NMES on the developing neuromuscular system.