Histology of Muscle Development in Pigs, Epigenetics from Myotubes to Tapered Fibres

Pre-natal muscle development in pigs starts with myotubes (axial nuclei in a tube of myofibrils) and secondary fibres (peripheral nuclei on an axial strand of myofibrils). By the time of birth, the nuclei of myotubes move to a peripheral position like secondary fibres. As pre-natal secondary fibres grow in length, the number of fibres in a transverse section may appear to increase. This stereology may also occur in post-natal muscles that have tapered fibres anchored in endomysial connective tissue around adjacent fibres and with one or both ends not reaching the end of their fasciculus. Up to 100 days gestation, Peroneus longus (no tapered fibres) had larger (P < 0.001) diameter secondary fibres than Longissimus thoracis (with tapered fibres). Up to 100 days gestation, no radial growth of secondary fibres was detected, but myotubes decreased in diameter (P < 0.001). From a curve showing the relative numbers of myotubes and secondary fibres, it was deduced that approximately 80% of muscle fibres in pigs are derived from secondary fibres. In post-natal Sartorius muscle there was an increase (P < 0.005) in the apparent number of muscle fibres attributed to longitudinal growth of tapered fibres. Myotubes located centrally within their fasciculi had the same position as slow-contracting fibres with a high myoglobin content in adult muscle. Post-natal changes in muscle fibre histochemistry were achieved through transitional types, probably neurally regulated rather than by differential longitudinal growth of tapered endings. Secondary fibres are important – they give rise to both the majority of muscle fibres in adult pigs and affect subsurface optical pathways and pork colourimetry.

Ciliary Hedgehog signaling patterns the digestive system to generate mechanical forces driving elongation

How tubular organs elongate is poorly understood. We found that attenuated ciliary Hedgehog signaling in the gut wall impaired patterning of the circumferential smooth muscle and inhibited proliferation and elongation of developing intestine and esophagus. Similarly, ablation of gut-wall smooth muscle cells reduced lengthening. Disruption of ciliary Hedgehog signaling or removal of smooth muscle reduced residual stress within the gut wall and decreased activity of the mechanotransductive effector YAP. Removing YAP in the mesenchyme also reduced proliferation and elongation, but without affecting smooth muscle formation, suggesting that YAP interprets the smooth muscle-generated force to promote longitudinal growth. Additionally, we developed an intestinal culture system that recapitulates the requirements for cilia and mechanical forces in elongation. Pharmacologically activating YAP in this system restored elongation of cilia-deficient intestines. Thus, our results reveal that ciliary Hedgehog signaling patterns the circumferential smooth muscle to generate radial mechanical forces that activate YAP and elongate the gut.

Dynamic Changes in Serum IGF-I and Growth During Infancy: Associations to Body Fat, Target Height, and PAPPA2 Genotype

Context IGF-I is important for postnatal growth and may be of diagnostic value in infants suspected of pituitary disease; however, little is known about the impact of IGF-I and its determinants on infant growth. Importantly, detailed reference ranges for IGF-I and IGF binding protein-3 (IGFBP-3) concentrations during infancy are lacking. Objective To evaluate the rapid changes in weight and length as well as their determinants in healthy infants, and to establish age- and sex-specific reference curves for IGF-I and IGFBP-3 in children aged 0 to 1 years. Design Prospective longitudinal study. Setting Cohort study. Participants A total of 233 healthy children (114 girls) with repeated blood samples during the first year of life. Main Outcome Measure(s) Serum concentrations of IGF-I and IGFBP-3, length velocity, weight velocity, and PAPPA2 (rs1325598) genotype. Results Individual trajectories of length and weight velocities were sex specific. We provide detailed reference curves based on longitudinal data for IGF-I and IGFBP-3 during infancy. In both girls and boys, IGF-I decreased during infancy, whereas IGFBP-3 remained stable. IGF-I and IGFBP-3, but not PAPPA2 genotype, were positively associated with weight gain, but not with longitudinal growth. When stratified by sex, the association between weight gain and IGF-I only remained significant in girls. Conclusions Interestingly, we found a significant association between IGF-I and infant weight gain in girls, but not with longitudinal growth in the first year of life. Our findings highlight the role of IGF-I as an important anabolic hormone that is not limited to linear growth.

Does bribing lead to extra convenience or is it a barrier to longitudinal growth? Empirical evidence from South American Firms

Purpose This paper aims to study how firms’ longitudinal and dynamic growth will be affected by their bribing decisions to address the controversies existing in the extant literature on the impacts of briberies. Design/methodology/approach The authors acquired information from Enterprise Survey by the World Bank and compiled a unique panel data set including firms from five South American countries between 2006 and 2017. The authors used multiple methods to estimate firms’ productivity. A comprehensive inspection of firms’ longitudinal development using a two-step estimation method that addressed the endogeneity issue was then conducted. Findings Bribery could significantly shorten the waiting time for resources to become available. However, bribery also substantially and robustly slows down firms’ productivity growth over time. Meanwhile, a bribing firm is very likely to bribe again in the future. Originality/value This paper contributes to the extant literature by pioneering the empirical study of firms’ bribing decisions and their longitudinal growth. First, the authors constructed unique panel data and established a longitudinal investigation upon firms’ dynamic growth after bribing, filling the literature gap by studying the time-lagging effect of bribery on firms’ growth. Second, the authors performed a comprehensive overview of South American firms’ growth by looking into the dynamics of their production, employment, resource delay and productivity across years. Third, the authors found that bribing exerted contingent impacts upon firms’ growth, reconciling the mixed evidence in the literature.

On the Shape of Nucleons at High Energies

A scenario of the evolution of the shape of nucleons with increasing energy is described in the framework of an extended parton model, which consistently takes into account the transverse motion of the partons. At the energy E up to LHC, the nucleons have the form of a spheroid which expands as lnE in the transverse directions and grows linearly in E in the longitudinal direction. With a further increase in the energy, a mode of correlated behavior of the partons is established, which stops the longitudinal growth. Simultaneously, the expansion in the transverse directions changes to lnE, and a hollow mostly free of partons is formed inside the nucleons along the central axis in the direction of their motion. Numerical estimates of the corresponding parameters are obtained.

G-Protein-Coupled Estrogen Receptor-1 Positively Regulates the Growth Plate Chondrocyte Proliferation in Female Pubertal Mice

Estrogen enhances long bone longitudinal growth during early puberty. Growth plate chondrocytes are the main cells that contribute to long bone elongation. The role of G-protein-coupled estrogen receptor-1 (GPER-1) in regulating growth plate chondrocyte function remains unclear. In the present study, we generated chondrocyte-specific GPER-1 knockout (CKO) mice to investigate the effect of GPER-1 in growth plate chondrocytes. In control mice, GPER-1 was highly expressed in the growth plates of 4- and 8-week-old mice, with a gradual decline through 12 to 16 weeks. In CKO mice, the GPER-1 expression in growth plate chondrocytes was significantly lower than that in the control mice (80% decrease). The CKO mice also showed a decrease in body length (crown–rump length), body weight, and the length of tibias and femurs at 8 weeks. More importantly, the cell number and thickness of the proliferative zone of the growth plate, as well as the thickness of primary spongiosa and length of metaphysis plus diaphysis in tibias of CKO mice, were significantly decreased compared with those of the control mice. Furthermore, there was also a considerable reduction in the number of proliferating cell nuclear antigens and Ki67-stained proliferating chondrocytes in the tibia growth plate in the CKO mice. The chondrocyte proliferation mediated by GPER-1 was further demonstrated via treatment with a GPER-1 antagonist in cultured epiphyseal cartilage. This study demonstrates that GPER-1 positively regulates chondrocyte proliferation at the growth plate during early puberty and contributes to the longitudinal growth of long bones.

Using linear and natural cubic splines, SITAR, and latent trajectory models to characterise nonlinear longitudinal growth trajectories in cohort studies

Longitudinal data analysis can improve our understanding of the influences on health trajectories across the life-course. There are a variety of statistical models which can be used, and their fitting and interpretation can be complex, particularly where there is a nonlinear trajectory. This paper provides a guide to describing nonlinear growth trajectories for repeatedly measured continuous outcomes using linear mixed-effects (LME) models with linear splines and natural cubic splines, nonlinear mixed effects Super Imposition by Translation and Rotation (SITAR) models, and latent trajectory models. The underlying model for each of the four approaches, the similarities and differences between models, and their advantages and disadvantages are described. Their applications and correct interpretation are illustrated by analysing repeated bone mass measures across three cohort studies with 8,500 individuals and 37,000 measurements covering ages 5-40 years. Linear and natural cubic spline LME models and SITAR provided similar descriptions of the mean bone growth trajectory and growth velocity, and the sex differences in growth patterns. Latent trajectory models identified up to four subgroups of individuals with distinct trajectories during adolescence and similar trajectories in childhood and adulthood. Recommendations for choosing a modelling approach are provided along with a discussion and signposting on further modelling extensions for analysing trajectory exposures and outcomes, and multiple cohorts. In summary, we present a resource for characterising nonlinear longitudinal growth trajectories, that could be adapted for other complex traits. Scripts and synthetic datasets are provided so readers can replicate trajectory modelling and visualisation using the open-source R software.

Growth Patterns in Children With Multiple Endocrine Neoplasia Type 2B: Small Stature in Childhood

Background: Multiple Endocrine Neoplasia 2B (MEN2B) is characterized by medullary thyroid carcinoma (MTC) before the age of one, pheochromocytoma and several non-endocrine manifestations. Marfanoid habitus is considered to be an important related feature, leading to the assumption that children with MEN2B have a tall stature. However, very little is known about actual growth patterns in children with MEN2B and its implication for final height. Aim: To describe the growth patterns during childhood and adolescence and relate final height to target height (TH) in MEN2B patients. Methods: Growth during childhood was investigated in eight patients with MEN2B under care in a Dutch MEN expertise center. Growth charts were assessed in relation to parental height, age at diagnosis and at thyroidectomy, body mass index (BMI), pubertal development and extensiveness of disease manifestations. Results: Four out of eight patients showed longitudinal growth below their TH range. Three others showed prepubertal growth in the lowest margin of their TH range. Small stature was accompanied by delayed bone maturation. Arm span to height ratio was not increased in any of the (six) patients studied. All four patients who reached adulthood attained final height within their TH range, despite small stature during childhood. Small stature in childhood was not associated with age at diagnosis, age at thyroidectomy, extensiveness of MTC, BMI or endocrine deficiencies. Conclusions: Children with MEN2B did not present with marfanoid features regarding height or arm span. In contrary, short stature may be prevalent, with longitudinal growth beneath the individual TH range. Nevertheless, a normal final height within the TH range may well be reached. Growth patterns seem to be independent of both age at diagnosis and thyroidectomy as well as disease severity.