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Background: A database of normative quantitative measures of regional thoracic ventilatory dynamics, which is essential to understanding better thoracic growth and function in children, does not exist., Research Question: How to quantify changes in the components of ventilatory pump dynamics during childhood via thoracic quantitative dynamic MRI (QdMRI)?, Study Design and Methods: Volumetric parameters were derived via 51 dynamic MRI scans for left and right lungs, hemidiaphragms, and hemichest walls during tidal breathing. Volume-based symmetry and functional coefficients were defined to compare left and right sides and to compare contributions of the hemidiaphragms and hemichest walls with tidal volumes (TVs). Statistical analyses were performed to compare volume components among four age-based groups., Results: Right thoracic components were significantly larger than left thoracic components, with average ratios of 1.56 (95% CI, 1.41-1.70) for lung TV, 1.81 (95% CI, 1.60-2.03) for hemidiaphragm excursion TV, and 1.34 (95% CI, 1.21-1.47) for hemichest wall excursion TV. Right and left lung volumes at end-expiration showed, respectively, a 44% and 48% increase from group 2 (8 ≤ age < 10) to group 3 (10 ≤ age < 12). These numbers from group 3 to group 4 (12 ≤ age ≤ 14) were 24% and 28%, respectively. Right and left hemichest wall TVs exhibited, respectively, 48% and 45% increases from group 3 to group 4., Interpretation: Normal right and left ventilatory volume components have considerable asymmetry in morphologic features and dynamics and change with age. Chest wall and diaphragm contributions vary in a likewise manner. Thoracic QdMRI can provide quantitative data to characterize the regional function and growth of the thorax as it relates to ventilation., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: Both excessive and restricted fetal growth are associated with changes in cardiac geometry and function at birth. There are significant issues when indexing cardiac parameters for body size in the neonatal period. The aims of this study were to determine to what extent cardiac geometry is dependent on body size in term and preterm neonates with restricted or excessive fetal growth and how this is affected by adiposity., Methods: This was a cross-sectional study of neonates born between 31 and 42 weeks of gestation, divided into three groups: (1) small-for-gestational age (SGA, birth weight > 2 SD below the mean); (2) large-for-gestational age (LGA, birth weight > 2 SD above the mean); and (3) appropriate-for-gestational-age controls (AGA, birth weight ≤ 2 SD from the mean). Cardiac geometry and function were compared between the study groups, adjusting for body size. The potential impact of infant adiposity and maternal disease was assessed., Results: In total, 174 neonates were included, of which 39 were SGA, 45 were LGA and 90 were AGA. Body size was reflected in cardiac dimensions, with differences in cardiac dimensions disappearing between the SGA and AGA groups when indexed for body surface area (BSA) or thoracic circumference. The same was true for the differences in atrial and ventricular areas between the LGA and AGA groups. However, left ventricular inflow and outflow tract dimensions did not follow this trend as, when indexed for BSA, they were associated negatively with adiposity, resulting in diminished dimensions in LGA compared with AGA and SGA neonates. Adiposity was associated positively with left ventricular mass, right ventricular length and area and right atrial area. The SGA group showed increased right ventricular fractional area change, possibly reflecting differences in the systolic function of the right ventricle. We found evidence of altered diastolic function between the groups, with the mitral valve inflow E- to lateral E'-wave peak velocity ratio being increased in the LGA group and decreased in the SGA group., Conclusions: Cardiac geometry is explained by body size in both term and preterm AGA and SGA infants. However, the nature of the relationship between body size and cardiac dimensions may be influenced by adiposity in LGA infants, leading to underestimation of left ventricular inflow and outflow tract dimensions when adjusted for BSA. Adjustments for thoracic circumference provide similar results to those for BSA. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To determine internipple distance and internipple index in prepubertal Turkish girls., Methods: The internipple distance and chest circumference of 667 healthy prepubertal Turkish girls aged 6 to 11 years were measured in a school screening program in Düzce. Measurements were performed at the end of expiration with a standard non-stretch tape measure graduated in millimeters with the arms hanging in a relaxed position on the sides of the body. The internipple distance was measured between the centers of both nipples, and chest circumference was measured across the internipple line. The internipple index was calculated by dividing the internipple distance (cm) x100 by the chest circumference (cm). Age specific internipple index reference curves were constructed and smoothed with the Lambda-Mu-Sigma method. Mean and standard deviations of internipple distance and internipple index were calculated according to decimal ages., Results: Age was found to be positively correlated with internipple distance and chest circumference, while it was negatively correlated with internipple index. The reference values of internipple index, including 3 rd , 10 th , 25 th , 50 th , 75 th , 90 th , and 97 th percentiles, and standard deviations were calculated for prepubertal girls., Conclusion: The reference ranges provided by this study might be helpful for the evaluation of syndromic cases by serving as normative data for internipple index in prepubertal girls aged 6-11 years in Turkey although ethnic differences may affect applicability to other countries.

Background: Severe early-onset scoliosis leads to deficient spine height, thoracic growth inhibition, and ultimately pulmonary compromise. Rib-based growing instrumentation seeks to correct thoracic deformities, in part by correcting the spinal deformity, adding height, increasing thoracic volume, and allowing for continual spinal growth until maturity. However, the amount of growth in these patients relative to their peers is unknown., Methods: Sixty patients who had undergone surgical intervention for the treatment of early-onset scoliosis were assessed via radiographic measurements of coronal T1-S1 height and major curve angle before implantation and again at most recent follow-up (minimum 2 years). T1-S1 measurements were then compared with age-matched peers to assess growth differences. Clinical information was examined for relevant parameters., Results: The average age of our cohort at initial surgery and most recent follow-up was 4.4±3.8 and 10.0±4.4 years old, respectively. In this patient set, there was an average increase in T1-S1 height of 13.1±11.1 mm per year, with the majority of growth occurring in the first 2 years following implantation, and improvement in a major curve from 68±8 to 53±7 degrees. Overall, 77% of patients saw improvement in the major curve at most recent follow-up. Furthermore, a statistically significant greater percent of expected growth was seen in congenital compared with neuromuscular scoliosis (P<0.001). In addition, a weak negative correlation was observed between a number of surgical lengthenings and T1-S1 growth., Conclusions: Rib-based implant intervention has been shown to improve the major curve, but only improves growth potential to around 80% of expected growth. Scoliosis diagnosis type also influences growth rate potential, with congenital scoliosis patients being surgically treated earlier in life and having a growth rate approaching that of a healthy individual., Level of Evidence: Level III-Case control.

Sexual dimorphism is an important feature of adult thorax morphology, but when and how sex-related differences in the ribcage arise during ontogeny is poorly known. Previous research proposed that sex-related size differences in the nasal region arise during puberty. Therefore, we explore whether ribcage sexual dimorphism also arises at that time and whether this sexual dimorphism is maintained until old age. We measured 526 (semi)landmarks on 80 CT-based human ribcage reconstructions, on individuals ranging from 7 to 65 year-old. The 3D coordinates were submitted to the Procrustes superimposition and analyzed. Our results show that the trajectories of thorax size and shape between sexes diverge at around 12 years of age, and continue slightly diverging until old age. The differential ontogenetic trends cause adult male ribcages to become deeper, shorter, and wider than female. Our results are consistent with the evidence from the cranial respiratory system, with the development of sexual dimorphism probably related to changes in body composition during puberty combined with changes in the reproductive system.

Spatiotemporal changes in epithelial cell sizes-or epithelial cell size dynamics (ECD)-during morphogenesis entail interplay between two opposing forces: cell contraction via actomyosin cytoskeleton and cell expansion via cell-cell adhesion. Cell-cell adhesion-based ECD, however, has not yet been clearly demonstrated. For instance, changing levels of homophilic E-cadherin-based cell-cell adhesion induce cell sorting, but not ECD. Here we show that cell-expansive forces of heterophilic cell-cell adhesion regulate ECD: higher cell-cell adhesion results in cell size enlargement. Thus, ECD during morphogenesis in the heminotal epithelia of Drosophila pupae leading to thorax closure corresponds with spatiotemporal gradients of two heterophilic atypical cadherins-Fat (Ft) and Dachsous (Ds)-and the levels of Ft-Ds heterodimers formed concomitantly. Our mathematical modeling and genetic tests validate this mechanism of dynamic heterophilic cell-cell adhesion-based regulation of ECD. Conservation of these atypical cadherins suggests a wider prevalence of heterophilic cell-cell adhesion-based ECD regulation during animal morphogenesis.

Drosophila underreplicate the DNA of thoracic nuclei, stalling during S phase at a point that is proportional to the total genome size in each species. In polytene tissues, such as the Drosophila salivary glands, all of the nuclei initiate multiple rounds of DNA synthesis and underreplicate. Yet, only half of the nuclei isolated from the thorax stall; the other half do not initiate S phase. Our question was, why half? To address this question, we use flow cytometry to compare underreplication phenotypes between thoracic tissues. When individual thoracic tissues are dissected and the proportion of stalled DNA synthesis is scored in each tissue type, we find that underreplication occurs in the indirect flight muscle, with the majority of underreplicated nuclei in the dorsal longitudinal muscles (DLM). Half of the DNA in the DLM nuclei stall at S phase between the unreplicated G0 and fully replicated G1. The dorsal ventral flight muscle provides the other source of underreplication, and yet, there, the replication stall point is earlier (less DNA replicated), and the endocycle is initiated. The differences in underreplication and ploidy in the indirect flight muscles provide a new tool to study heterochromatin, underreplication and endocycle control.

Insect allatotropin (AT) plays multi-functions including regulation of juvenile hormone synthesis, growth, development and reproduction. In the present study, the full-length cDNA encoding the AT receptor was cloned from the brain of Helicoverpa armigera (Helar-ATR). The ORF of Helar-ATR exhibited the characteristic seven transmembrane domains of the G protein-coupled receptor (GPCR) and was close to the ATR of Manduca sexta in the phylogenetic tree. The Helar-ATR expressed in vertebrate cell lines can be activated by Helar-AT and each Helar-ATL in a dose-responsive manner, in the following order: Helar-ATLI > Helar-ATLII > Helar-AT > Helar-ATLIII. Helar-ATLI and Helar-ATLII represented the functional ligands to Helar-ATR in vitro, while Helar-AT and Helar-ATLIII behaved as partial agonists. The in vitro functional analysis suggested that the Helar-ATR signal was mainly coupled with elevated levels of Ca 2+ and independent of cAMP levels. Helar-ATR mRNA in larvae showed the highest level in the brain, followed by the thorax ganglion, abdomen ganglion, fat body and midgut. Helar-ATR mRNA levels in the complex of the brain-thoracic-abdomen ganglion on the 2nd day of the larval stage and during later pupal stages were observed to be relatively higher than in the wandering and early pupal stages., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Perilipins are evolutionarily conserved from insects to mammals. Lipid storage droplet-1 (LSD-1) is a member of the lipid droplet's surface-binding protein family and counterpart to mammalian perilipin 1. The role of LSD-1 has already been reported in lipid metabolism of Drosophila. However, the function of this gene during specific tissue development is still under investigation. Here, we found that LSD-1 is expressed in the notum of the wing imaginal disc, and notum-specific knockdown of Lsd-1 by pannir-GAL4 driver leads to split thorax phenotype in adults, suggesting an essential role of LSD-1 in development of Drosophila thorax. As overexpression of JNK homolog, bsk (basket) suppresses Lsd-1 knockdown phenotype, the role of LSD-1 in thorax development was proved to be dependent on the activity of the Drosophila c-Jun N-terminal kinase (JNK). The puckered (puc) expression led to significant decrease in the JNK activity in wing discs of Lsd-1 knockdown flies. In addition, we also detected that depletion of Lsd-1 enhances apoptotic cell death in the wing notum area. Taken together, these data demonstrated that LSD-1 functions in Drosophila thorax development by regulating JNK pathway., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Early-onset scoliosis (EOS) is defined as the diagnosis of a spinal deformity before the age of 5 years. It can be divided into idiopathic, neuromuscular/syndromic, and congenital etiologies., Methods: The literature on the natural history of EOS was summarized., Results: The natural history varies with the etiology of EOS. Idiopathic curves may benefit from early serial casting. The natural history of neuromuscular and syndromic scoliosis is highly dependent on the natural history of the underlying disorder. Congenital scoliosis has a variable prognosis depending on the location and extent of the congenital malformations., Conclusions: Treatment of children with EOS is customized to the particular disorder. While lack of treatment has been shown to lead to increased mortality, extensive early definitive fusion may lead to thoracic insufficiency. Delaying definitive surgery and the use of growing instrumentation may provide benefit in maintaining pulmonary health., Clinical Relevance: Potential disturbance of growth must be considered in the treatment of young children with scoliosis.

As larval cannibalism is common under intensive rearing conditions, leg regeneration can help ladybugs adapt to the competitive environment, but whether the leg regeneration leads to side effects on development remains unclear. To analyze the potentially developmental cost of leg regeneration, the developmental period and weight of leg-regenerated Coccinella septempunctata were studied in the laboratory. The results showed that, when the time intervals between the emergency of 4th-instar larva and leg amputation increased, the developmental period of leg-regenerated 4th-instar larvae was gradually prolonged. Significantly developmental delay were also examined at prepupal and pupal stages, and various timings of leg amputation affected the periods of leg-regenerated prepupae/pupae similarly. After the leg was amputated at different larval instars, the developmental delay only occurred at the larval instar when the leg was amputated, whereas other larval instars failed to be extended, and the developmental periods of leg-regenerated prepupae/pupae were affected similarly by the instars of leg amputation. Developmental delays possibly resulted in more consumption by leg-regenerated larvae, and then weight gains at prepupal/pupal stages, but different larval instars of leg amputation affected the weight gain similarly. Both the developmental delay (at 4th-instar larval, prepupal and pupal stages) and weight gain (at pupal and adult stages) in complete/bilateral amputation were longer or greater than those in half/unilateral amputation. However, the thoracic locations of leg amputation impacted the developmental delay and weight gain similarly. Our study indicates that although leg regeneration triggers the developmental cost decreasing the competitive superiority or agility, C. septempunctata larvae still choose to completely regenerate the leg to adapt to complex environments. Thus, in order to remain competitive at adult stages, leg-impaired larvae may make an investment tradeoff between leg regeneration and developmental cost., Competing Interests: The authors have declared that no competing interests exist.

In epithelial tissue, new cell-cell junctions are formed upon cytokinesis. To understand junction formation during cytokinesis, we explored de novo formation of tricellular septate junctions (TCJs) in Drosophila epithelium. We found that upon midbody formation, the membranes of the two daughter cells and of the neighbouring cells located below the adherens junction (AJ) remain entangled in a 4-cell structure apposed to the midbody. The septate junction protein Discs-Large and components of the TCJ, Gliotactin and Anakonda accumulate in this 4-cell structure. Subsequently, a basal movement of the midbody parallels the detachment of the neighbouring cell membranes from the midbody, the disengagement of the daughter cells from their neighbours and the reorganisation of TCJs between the two daughter cells and their neighbouring cells. While the movement of midbody is independent of the Alix and Shrub abscission regulators, the loss of Gliotactin or Anakonda function impedes both the resolution of the connection between the daughter-neighbour cells and midbody movement. TCJ proteins therefore control an additional step of cytokinesis necessary for the disentanglement of the daughter cells from their neighbours during cytokinesis., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Prion protein (PRNP) gene is well known for affecting mammal transmissible spongiform encephalopathies (TSE), and is also reported to regulate phenotypic traits (e.g. growth traits) in healthy ruminants. To identify the insertion/deletion (indel) variations of the PRNP gene and evaluate their effects on growth traits, 768 healthy individuals from five sheep breeds located in China and Mongolia were identified and analyzed. Herein, four novel indel polymorphisms, namely, Intron-1-insertion-7bp (I1-7bp), Intron-2-insertion-15bp (I2-15bp), Intron-2-insertion-19bp (I2-19bp), and 3' UTR-insertion-7bp (3' UTR-7bp), were found in the sheep PRNP gene. In five analyzed breeds, the minor allelic frequencies (MAF) of the above indels were in the range of 0.008 to 0.986 (I1-7bp), 0.113 to 0.336 (I2-15bp), 0.281 to 0.510 (I2-19bp), and 0.040 to 0.238 (3' UTR-7bp). Additionally, there were 15 haplotypes and the haplotype 'I I2-15bp -D 3'UTR-7bp -D I2-19bp -D I1-7bp ' had the highest frequency, which varied from 0.464 to 0.629 in five breeds. Moreover, association analysis revealed that all novel indel polymorphisms were significantly associated with 13 different growth traits (P < 0.05). Particularly, the influences of I2-15bp on chest width (P = 0.001) in Small Tail Han sheep (ewe), 3' UTR-7bp on chest circumference (P = 0.003) in Hu sheep, and I2-19bp on tail length (P = 0.001) in Tong sheep, were highly significant (P < 0.01). These findings may be a further step toward the detection of indel-based typing within and across sheep breeds, and of promising target loci for accelerating the progress of marker-assisted selection in sheep breeding.

Objective: Ververck index (VI) reflects thoracic development, body type, and nutritional status. This study aimed to investigate the VI of singleton neonates with a gestational age (GA) of 27-42 weeks at birth, and to establish percentile curves of VI of the neonates., Methods: Cross-sectional cluster sampling was performed between April 2013 and September 2015. Body weight, body length, and chest circumference were measured for 16 865 singleton neonates with a GA of 27-42 weeks in two hospitals in Shenzhen, China. VI was calculated and the percentile curves of VI were plotted for the neonates., Results: Mean VIs were obtained for singleton neonates with a gestational age of 27-42 weeks (in three groups of male, female, and both sexes), and related 3rd-97th percentile curves were plotted. As for the 50th percentile curve, the singleton neonates with a GA of 27 weeks had the lowest 50th percentile value of VI, which gradually increased with the increase in GA. The singleton neonates with a GA of 42 weeks had the highest 50th percentile value of VI. Girls had a slightly higher 50th percentile value of VI than boys in all GA groups., Conclusions: VI of neonates increases with the increase in GA. Female neonates may have a slightly better thoracic development, body type, and nutritional status than male neonates at birth. The percentile curves of VI plotted for singleton neonates with a GA of 27-42 weeks (in three groups of male, female, and both sexes) can provide a basis for evaluating thoracic development, body type, and nutritional status of neonates at birth in Shenzhen, China.

When male animals engage in intrasexual contests then any alternative tactics they use can be associated with dimorphisms in the expression of weapons. Some species have recently been found to exhibit trimorphism in their weaponry, suggesting that the processes leading to their evolution and maintenance of these polymorphisms can be more complex than previously thought. Here, we describe the extraordinary diversity of polymorphism within the genus Odontolabis: there are dimorphic species (O. siva and O. platynota), trimorphic species (O. cuvera, as previously described, and O. sommeri s.stricto) and, uniquely, tetramorphic species, with males of O. sommeri lowei and O. brookeana showing four clearly differentiated male morphs: small "Gammas", "Alphas" which express large, long mandibles, "Betas" which have long mandibles with different morphology and "Boltcutters", with short, wide mandibles. Such polymorphisms are usually thought of as being maintained as a status-dependent conditional strategy, but we found only one size threshold: in most cases males develop into Gamma males below a certain size but there is no relationship between morph and body size amongst the larger, 'weaponised' morphs. We suggest that the complex polymorphisms in these animals are probably maintained by a combination of a conditional strategy and a genetic polymorphism.

The proto-oncogene Myc is well known for its roles in promoting cell growth, proliferation and apoptosis. However, in this study, we found from a genetic screen that Myc inhibits, rather than promotes, cell death triggered by c-Jun N-terminal kinase (JNK) signaling in Drosophila. Firstly, expression of Drosophila Myc (dMyc) suppresses, whereas loss of dMyc enhances, ectopically activated JNK signaling-induced cell death. Secondly, dMyc impedes physiologically activated JNK pathway-mediated cell death. Thirdly, loss of dMyc triggers JNK pathway activation and JNK-dependent cell death. Finally, the mammalian cMyc gene, when expressed in Drosophila, impedes activated JNK signaling-induced cell death. Thus, besides its well-studied apoptosis promoting function, Myc also antagonizes JNK-mediated cell death in Drosophila, and this function is likely conserved from fly to human.

Background: Children with chronic kidney disease are frequently born small for gestational age (SGA) and prone to disproportionately short stature. It is unclear how SGA affects growth after kidney transplantation (KTx)., Methods: Linear growth (height, sitting height, and leg length) was prospectively investigated in a cohort of 322 pediatric KTx recipients, with a mean follow-up of 4.9 years. Sitting height index (ratio of sitting height to total body height) was used to assess body proportions. Predictors of growth outcome in KTx patients with (n = 94) and without (n = 228) an SGA history were evaluated by the use of linear mixed-effects models., Results: Mean z-scores for all linear body dimensions were lower in SGA compared with non-SGA patients (p < 0.001). SGA patients presented with higher target height deficit and degree of body disproportion (p < 0.001). The latter was mainly due to reduced leg growth during childhood. Pubertal trunk growth was diminished in SGA patients, and the pubertal growth spurt of legs was delayed in both groups, resulting in further impairment of adult height, which was more frequently reduced in SGA than in non-SGA patients (50 % vs 18 %, p < 0.001). Use of growth hormone treatment in the pre-transplant period, preemptive KTx, transplant function, and control of metabolic acidosis were the only potentially modifiable correlates of post-transplant growth in SGA groups. By contrast, living related KTx, steroid exposure, and degree of anemia proved to be correlates in non-SGA only., Conclusions: In children born SGA, growth outcome after KTx is significantly more impaired and affected by different clinical parameters compared with non-SGA patients.

The assembly of the musculoskeletal system in Drosophila relies on the integration of chemical and mechanical signaling between the developing muscles with ectodermal cells specialized as "tendon cells." Mechanical tension generated at the junction of flight muscles and tendon cells of the notum epithelium is required for muscle morphogenesis, and is balanced by the epithelium in order to not deform. We report that Drosophila Rho kinase (DRok) is necessary in tendon cells to assemble stable myotendinous junctions (MTJ), which are required for muscle morphogenesis and survival. In addition, DRok is required in tendon cells to maintain epithelial shape and cell orientation in the notum, independently of chascon (chas). Loss of DRok function in tendon cells results in mis-orientation of tendon cell extensions and abnormal accumulation of Thrombospondin and βPS-integrin, which may cause abnormal myotendinous junction formation and muscle morphogenesis. This role does not depend exclusively on nonmuscular Myosin-II activation (Myo-II), indicating that other DRok targets are key in this process. We propose that DRok function in tendon cells is key to promote the establishment of MTJ attachment and to balance mechanical tension generated at the MTJ by muscle compaction., (Copyright © 2016 by the Genetics Society of America.)

The Haller index is a ratio of thoracic width and height, measured from an axial CT image and used to describe the internal dimensions of the thoracic cage. Although the Haller index for a normal thorax has been established (Haller et al. 1987; Daunt et al. 2004), this is only at one undefined vertebral level in the thorax. What is not clear is how the Haller index describes the thorax at every vertebral level in the absence of sternal deformity, or how this is affected by age. This paper documents the shape of the thorax using the Haller index calculated from the thoracic width and height at all vertebral levels of the thorax between 8 and 18 years of age. The Haller Index changes with vertebral level, with the largest ratio seen in the most cranial levels of the thorax. Increasing age alters the shape of the thorax, with the most cranial vertebral levels having a greater Haller index over the mid thorax, which does not change. A slight increase is seen in the more caudal vertebral levels. These data highlight that a 'one size fits all' rule for chest width and depth ratio at all ages and all thoracic levels is not appropriate. The normal range for width to height ratio should be based on a patient's age and vertebral level., (© 2016 Anatomical Society.)

The first three essential amino acids (EAA) for broilers including methionine (Met), lysine (Lys) and threonine (Thr) may greatly influence the growth of chick muscles at early stages of life. In order to survey the potential effects of those EAA on growth muscles, a rotatable three-variable central composite design (CCD) was conducted to track the interrelationships of dietary digestible Met (dMet), Lys (dLys) and Thr (dThr) for optimization of processing yields in broiler chicks using response surface methodology. A total of 60 floor pens of six birds each were assigned to 15 dietary treatments based on CCD containing five levels of dMet (0.416% to 0.584% of diet), dLys (0.881% to 1.319% of diet) and dThr (0.532% to 0.868% of diet) from 3 to 16 days of age. Experimental treatments significantly affected breast mass (BM) and leg mass (LM) of the birds (P<0.05) in which the main effect of dLys on BM was threefold higher than the main effect of dThr, and interaction effect between dMet and dLys was observed on BM (P<0.05). However, in the case of LM, the main effect of dThr was higher than the main effects of dMet and dLys and highest interaction effect exist between dThr and dMet (P<0.05). The second-order models for BM and LM were fitted by least squares regression. Canonical analysis revealed that the stationary points for carcass components were saddle points, thus ridge analysis was performed for getting optimal values of each EAA. Ridge analyses of BM and LM models showed that the maximum BM point may be obtained with 0.58%, 1.05% and 0.76% of dMet, dLys and dThr, respectively, in diet, and maximum LM point may be achieved with 0.58%, 1.09% and 0.70% of dMet, dLys and dThr, respectively, in diet. The resultant ideal ratios of dMet and dThr to dLys were 55% and 72% for BM; 53% and 64% for LM. Moreover, sensitivity analysis showed that the most important amino acids in BM and LM models were Lys and Thr, respectively. In conclusion, providing these three amino acid for BM optimization may warrant LM optimization and higher ideal ratios of dMet and dThr for breast muscle may indicate the higher importance of these EAA in this muscle than those in thigh muscle.

Altering incubation temperature during embryogenesis has an impact on chicken embryo growth, but the underlying molecular mechanisms are not understood; the present study was performed to address these changes. Broiler eggs were incubated at low (36.8°C), control (37.8°C), and high (38.8°C) temperatures between Embryonic Day (ED) 7 and 10 or ED 10 and 13, which cover critical periods of embryonic myogenesis. The embryos were then dissected immediately after treatment on ED 10 or 13 to assess body, liver, and heart weights as well as to analyze breast and leg muscle fibers for their mitochondrial respiratory activity (MRA). Breast muscle samples were additionally used to evaluate the activity of enzymes involved in energy metabolism and cell-cycle progression. ED-10 embryos incubated at 38.8°C showed elevated weights (body, liver, and heart), MRA, and activities of lactate dehydrogenase and cytochrome oxidase compared to the ED-10 embryos incubated at 36.8°C. Similarly, the ED-13 embryos incubated at 38.8°C showed elevated body weight, MRA, and activities of glycogen phosphorylase, phosphofructokinase, and cytochrome oxidase compared to their 36.8°C counterparts. Embryos incubated at the normal temperature (37.8°C), however, showed variable differences from those incubated at 38.8°C versus 36.8°C. Cell-cycle enzyme activities were not impacted by the different temperature treatments. Thus, an increase or decrease in the incubation temperature during embryonic broiler myogenesis results in altered embryo activity, muscle energy metabolism, and activity-dependent muscle growth., (© 2015 Wiley Periodicals, Inc.)

The thoracic-to-hip circumference ratio (THR) is an anthropometric marker recently described as a predictor of type 2 diabetes. In this study, we performed a genome-wide association study (GWAS) followed by confirmatory analyses to identify genetic markers associated with THR. A total of 7,240 Korean subjects (4,988 for the discovery stage and 2,252 for the confirmatory analyses) were recruited for this study, and genome-wide single nucleotide polymorphism (SNP) genotyping of the initial 4,988 individuals was performed using Affymetrix Human SNP array 5.0. Linear regression analysis was then performed to adjust for the effects of age, sex, and current diabetes medication status on the THR of the study subjects. In the initial discovery stage, there was a statistically nominal association between minor alleles of SNP markers on chromosomes 4, 8, 10, and 12, and THR changes (p < 5.0 × 10-6). The subsequent confirmatory analyses of these markers, however, only detected a significant association between two SNPs in the HECTD4 gene and decreased THRs. Notably, this association was detected in male (rs11066280: p = 1.14 × 10-2; rs2074356: p = 1.10 × 10-2), but not in female subjects. Meanwhile, the combined results from the two analyses (initial and confirmatory) indicated that minor alleles of these two intronic variants exhibited a significant genome-wide association with decreased THR in the male subjects (n = 3,155; rs11066280: effect size = -0.008624, p = 6.19 × 10-9; rs2074356: effect size = -0.008762, p = 1.89 × 10-8). Furthermore, minor alleles of these two SNPs exhibited protective effects on patients' risks for developing type 2 diabetes. In conclusion, we have identified two genetic variations in HECTD4 that are associated with THR, particularly in men.

Mechanisms that coordinate growth during development are essential for producing animals with proper organ proportion. Here we describe a pathway through which tissues communicate to coordinate growth. During Drosophila melanogaster larval development, damage to imaginal discs activates a regeneration checkpoint through expression of Dilp8. This both produces a delay in developmental timing and slows the growth of undamaged tissues, coordinating regeneration of the damaged tissue with developmental progression and overall growth. Here we demonstrate that Dilp8-dependent growth coordination between regenerating and undamaged tissues, but not developmental delay, requires the activity of nitric oxide synthase (NOS) in the prothoracic gland. NOS limits the growth of undamaged tissues by reducing ecdysone biosynthesis, a requirement for imaginal disc growth during both the regenerative checkpoint and normal development. Therefore, NOS activity in the prothoracic gland coordinates tissue growth through regulation of endocrine signals., (Copyright © 2015 by the Genetics Society of America.)

Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the overall steps in wound healing, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process. However, they do allow the less understood aspects of the healing response to be explored, e.g., which signal(s) are responsible for initiating tissue remodeling? How is sealing of the epithelia achieved? Or, what inhibitory cues cancel the healing machinery upon completion? Answering these and other questions first requires the identification and functional analysis of wound specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method that is healing-permissive and that allows live imaging and biochemical analysis of cultured imaginal discs. We performed comparative genome-wide profiling between Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. Sets of potential wound-specific genes were subsequently identified. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in healing assays. This non-saturated analysis defines a relevant set of genes whose changes in expression level are functionally significant for proper tissue repair. Amongst these we identified the TCP1 chaperonin complex as a key regulator of the actin cytoskeleton essential for the wound healing response. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound healing response.

Objective: Serial lengthening with growing rods is recommended every six months for the treatment of early onset scoliosis. The objective of this study was to evaluate the longitudinal growth of the thorax and control of the deformity in a series of patients with juvenile scoliosis when time intervals were increased between lengthenings., Material and Methods: Retrospective study of eight patients. The following variables were measured: the Cobb angle, the apical vertebral translation, the coronal balance, thoracic T1-L1 length, thoracic T5-T12 kyphosis, the proximal junctional kyphosis (PJK) angle, and the lumbar lordosis. Complications were recorded., Results: Five idiopathic and three syndromic scoliosis cases (mean age 9.4 ± 1.5 years) were evaluated. The initial surgery was followed by with an average of two distractions per patient. The mean time between distractions was 15.7 months. The final coronal main curve correction was 58%. Apical translation and coronal balance were improved and maintained after the surgeries. The thoracic (T1-L1) preoperative length was 20.8 cm, the postoperative length was 24.4 cm, and the final length was 26 cm. At the end of follow-up, the average growth of the thorax was 5.2 cm. The preoperative (T5-T12) kyphosis was 33.5°, and final 32.1°. The change in the PJK angle was 2.5° at the end of follow-up. Most complications were related to instrumentation. Two superficial wound infections were encountered., Conclusion: For less severe juvenile scoliosis patients treated with growing rods, spacing out lengthenings over more than a year can decrease the number of surgeries, while still controlling the deformity and allowing longitudinal thoracic growth., (Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.)

Epithelial morphogenesis is an essential process in all metazoans during both normal development and pathological processes such as wound healing. The coordinated regulation of cell shape, cell size, and cell adhesion during the migration of epithelial sheets ultimately gives rise to the diversity of body plans among different organisms as well as the diversity of cellular structures and tissues within an organism. Metamorphosis of the Drosophila pupa is an excellent system to study these transformative events. During pupal development, the cells of the wing imaginal discs migrate dorsally and fuse to form the adult thorax. Here I show centralspindlin, a protein complex well known for its role in cytokinesis, is essential for migration of wing disc cells and proper thorax closure. I show the subcellular localization of centralspindlin is important for its function in thorax development. This study demonstrates the emerging role of centralspindlin in regulating cell migration and cell adhesion in addition to its previously known function during cytokinesis., (© 2014 Wiley Periodicals, Inc.)

Background: Donor-site deformity may complicate autologous costal cartilage harvest for microtia reconstruction. This is reportedly prevented by total subperichondrial costal cartilage harvest, costochondral growth center preservation, donor-site reconstitution with morselized leftover costal cartilage, and perichondrial repair (Kawanabe-Nagata method). However, no quantitative assessment of preoperative versus postoperative thoracic morphology exists following use of this method., Methods: Twenty-five consecutive patients (11 adult and 14 growing patients) who received radiographic donor-site evaluation for autologous unilateral primary microtia reconstruction were studied. Each underwent thoracic three-dimensional computed tomography preoperatively and 6 months postoperatively. The authors quantified (1) donor-site skeletal deformation with respect to the sixth to ninth costochondral junctions (2) and distortion in thoracic/hemithoracic Haller indices. The contralateral unoperated hemithorax provided intrapatient control data., Results: Statistically significant deformations occurred in the sagittal and transverse planes in growing patients and in the transverse plane in adults, with respect to most costochondral junctions on operated versus unoperated sides. Importantly, in growing patients, the sixth to ninth costochondral junctions on the operated side failed to descend postoperatively with normal growth in the vertical plane, unlike on the unoperated side. However, no gross distortions in thoracic/hemithoracic proportions occurred according to Haller indices., Conclusions: Despite meticulous donor-site management and reconstruction according to the Kawanabe-Nagata method, patients sustained significant localized skeletal deformations, as quantified by three-dimensional computed tomography, the configurations of which differed according to whether patients were adult or growing when operated on. Whether these improve or worsen in the long term, particularly in growing patients, requires confirmation., Clinical Question/level of Evidence: Therapeutic, III.

Study Design: Retrospective case series., Objective: To report the outcomes of distraction-based, growth-sparing spinal instrumentation in patients with skeletal dysplasia., Summary of Background Data: Patients with skeletal dysplasia with spinal deformity often undergo early fusion, further compromising an already small chest. Nonfusion techniques may provide a safe alternative and allow for thoracic growth., Methods: Between 2004 and 2010, 12 children with a diagnosis of various types of skeletal dysplasia underwent growth-sparing spinal instrumentation for severe spinal deformities. The mean duration of treatment with growing rods was 57 months (42-84 mo). Nine patients were treated with growing rods (8 dual, 1 single), and 3 were treated with vertical expandable prosthetic titanium rib (VEPTR; Synthes). Preoperative, initial postoperative, and final follow-up anteroposterior and lateral spine radiographs were measured for magnitude of deformity, junctional kyphosis, and implant failure., Results: The major curve Cobb angle improved from a mean of 79° preoperatively to a mean of 41° at the last follow-up (52%). There was a decrease in mean thoracic kyphosis from 77° preoperatively to 64° at final follow-up and an increase in mean lumbar lordosis from 58° preoperatively to 63° at final follow-up. The mean space available for the lungs increased by 26 mm on the concave and 24 mm on the convex side. Six patients required revision surgery for proximal junctional kyphosis. There were 4 rod failures and 6 hook and 8 screw dislodgements. One patient with vertical expandable prosthetic titanium rib had failed rib fixation that required revision., Conclusion: Growth-sparing spinal instrumentation in patients with skeletal dysplasia and severe spinal deformity has a high complication and revision rate, and surgeons should closely monitor these patients. The complication rate is comparable with previous reports on patients with other diagnoses. However, deformities were well controlled, some trunk growth was achieved, and fusion surgery was delayed in all cases., Level of Evidence: 4.

The difficulties in quantifying the 3D form and spatial relationships of the skeletal components of the ribcage present a barrier to studies of the growth of the thoracic skeleton. Thus, most studies to date have relied on traditional measurements such as distances and indices from single or few ribs. It is currently known that adult-like thoracic shape is achieved early, by the end of the second postnatal year, with the circular cross-section of the newborn thorax transforming into the ovoid shape of adults; and that the ribs become inclined such that their anterior borders come to lie inferior to their posterior. Here we present a study that revisits growth changes using geometric morphometrics applied to extensive landmark data taken from the ribcage. We digitized 402 (semi) landmarks on 3D reconstructions to assess growth changes in 27 computed tomography-scanned modern humans representing newborns to adults of both sexes. Our analyses show a curved ontogenetic trajectory, resulting from different ontogenetic growth allometries of upper and lower thoracic units. Adult thoracic morphology is achieved later than predicted, by diverse modifications in different anatomical regions during different ontogenetic stages. Besides a marked increase in antero-posterior dimensions, there is an increase in medio-lateral dimensions of the upper thorax, relative to the lower thorax. This transforms the pyramidal infant thorax into the barrel-shaped one of adults. Rib descent is produced by complex changes in 3D curvature. Developmental differences between upper and lower thoracic regions relate to differential timings and rates of maturation of the respiratory and digestive systems, the spine and the locomotor system. Our findings are relevant to understanding how changes in the relative rates of growth of these systems and structures impacted on the development and evolution of modern human body shape.

Establishment of planar cell polarity (PCP) in a tissue requires coordination of directional signals from cell to cell. It is thought that this is mediated by the core PCP factors, which include cell-adhesion molecules. Here, we demonstrate that furrowed, the Drosophila selectin, is required for PCP generation. Disruption of PCP in furrowed-deficient flies results from a primary defect in Fz levels and cell adhesion. Furrowed localizes at or near apical junctions, largely colocalizing with Frizzled and Flamingo (Fmi). It physically interacts with and stabilizes Frizzled, and it mediates intercellular Frizzled-Van Gogh (Vang)/Strabismus interactions, similarly to Fmi. Furrowed does so through a homophilic cell-adhesion role that is distinct from its known carbohydrate-binding function described during vertebrate blood-cell/endothelial cell interactions. Importantly, the carbohydrate function is dispensable for PCP establishment. In vivo studies suggest that Furrowed functions partially redundantly with Fmi, mediating intercellular Frizzled-Vang interactions between neighboring cells., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The insect exoskeleton provides shape, waterproofing, and locomotion via attached somatic muscles. The exoskeleton is renewed during molting, a process regulated by ecdysteroid hormones. The holometabolous pupa transforms into an adult during the imaginal molt, when the epidermis synthe3sizes the definitive exoskeleton that then differentiates progressively. An important issue in insect development concerns how the exoskeletal regions are constructed to provide their morphological, physiological and mechanical functions. We used whole-genome oligonucleotide microarrays to screen for genes involved in exoskeletal formation in the honeybee thoracic dorsum. Our analysis included three sampling times during the pupal-to-adult molt, i.e., before, during and after the ecdysteroid-induced apolysis that triggers synthesis of the adult exoskeleton., Results: Gene ontology annotation based on orthologous relationships with Drosophila melanogaster genes placed the honeybee differentially expressed genes (DEGs) into distinct categories of Biological Process and Molecular Function, depending on developmental time, revealing the functional elements required for adult exoskeleton formation. Of the 1,253 unique DEGs, 547 were upregulated in the thoracic dorsum after apolysis, suggesting induction by the ecdysteroid pulse. The upregulated gene set included 20 of the 47 cuticular protein (CP) genes that were previously identified in the honeybee genome, and three novel putative CP genes that do not belong to a known CP family. In situ hybridization showed that two of the novel genes were abundantly expressed in the epidermis during adult exoskeleton formation, strongly implicating them as genuine CP genes. Conserved sequence motifs identified the CP genes as members of the CPR, Tweedle, Apidermin, CPF, CPLCP1 and Analogous-to-Peritrophins families. Furthermore, 28 of the 36 muscle-related DEGs were upregulated during the de novo formation of striated fibers attached to the exoskeleton. A search for cis-regulatory motifs in the 5'-untranslated region of the DEGs revealed potential binding sites for known transcription factors. Construction of a regulatory network showed that various upregulated CP- and muscle-related genes (15 and 21 genes, respectively) share common elements, suggesting co-regulation during thoracic exoskeleton formation., Conclusions: These findings help reveal molecular aspects of rigid thoracic exoskeleton formation during the ecdysteroid-coordinated pupal-to-adult molt in the honeybee.

Objective: To determine the efficacy of growing rods in the treatment of early onset scoliosis., Material and Methods: A total of 32 patients were treated using fusion techniques that included double growing rods and Vertical Expandable Prosthetic Titanium Ribs (VEPTR), in our Early Onset Scoliosis Centre between 2004 and 2011. After analysing the clinical histories and x-rays, 20 patients were included due to meeting the inclusion criteria. All patients had previously received conservative treatment with cranial traction and a series of plasters/corsets. The deformity was analysed before and after the initial surgery, and in successive tightenings, using the x-rays of the coronal and sagittal planes by means of the Cobb angle, as well as the longitudinal and coronal growth of the thorax, and the growth of the spinal column. A series of 188 x-rays of 53 patients with cystic fibrosis were studied in order to perform a comparative analysis with the patients with early-onset scoliosis., Results: There was significant improvement in the angle (Cobb and kyphosis) and linear parameters (T1-S1 distance, T1-T12 distance, and coronal width of the thorax) after the initial surgery, but the successive tightenings had a minimal beneficial effect, losing effectiveness over a period of time. The patients with early-onset scoliosis showed a lower growth of the thorax compared to the patients with cystic fibrosis., Discussion: Treatment of early-onset scoliosis with expandable devices is mainly beneficial with the initial procedure and the first tightenings, but shows a loss of efficacy over a period time., (Copyright © 2012 SECOT. Published by Elsevier Espana. All rights reserved.)

How adhesive contacts with neighbors may affect epithelial cell cytokinesis is unknown. We report that in Drosophila, septins are specifically required for planar (but not orthogonal) cytokinesis. During planar division, cytokinetic furrowing initiates basally, resulting in a contractile ring displaced toward the adherens junction (AJ). The formation of new AJ between daughter cells requires the disengagement of E-Cadherin complexes between mitotic and neighboring cells at the cleavage furrow, followed by the assembly of E-Cadherin complexes on the daughter-daughter interface. The strength of adhesion with neighbors directly impacts both the kinetics of AJ disengagement and the length of the new AJ. Loss of septins causes a reduction in the contractility of the actomyosin ring and prevents local disengagement of AJ in the cleavage furrow. By modulating the strength of tension induced by neighbors, we uncover a mechanical function for septins to overcome the extrinsic tension induced by neighboring interphasic cells., (Copyright © 2013 Elsevier Inc. All rights reserved.)

How adherens junctions (AJs) are formed upon cell division is largely unexplored. Here, we found that AJ formation is coordinated with cytokinesis and relies on an interplay between the dividing cell and its neighbors. During contraction of the cytokinetic ring, the neighboring cells locally accumulate Myosin II and produce the cortical tension necessary to set the initial geometry of the daughter cell interface. However, the neighboring cell membranes impede AJ formation. Upon midbody formation and concomitantly to neighboring cell withdrawal, Arp2/3-dependent actin polymerization oriented by the midbody maintains AJ geometry and regulates AJ final length and the epithelial cell arrangement upon division. We propose that cytokinesis in epithelia is a multicellular process, whereby the cooperative actions of the dividing cell and its neighbors define a two-tiered mechanism that spatially and temporally controls AJ formation while maintaining tissue cohesiveness., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The Drosophila Jun N-terminal kinase (JNK) gene basket (bsk) promoter contains a DNA replication-related element (DRE)-like sequence, raising the possibility of regulation by the DNA replication-related element-binding factor (DREF). Chromatin immunoprecipitation assays with anti-DREF IgG showed the bsk gene promoter region to be effectively amplified. Luciferase transient expression assays revealed the DRE-like sequence to be important for bsk gene promoter activity, and knockdown of DREF decreased the bsk mRNA level and the bsk gene promoter activity. Furthermore, knockdown of DREF in the notum compartment of wing discs by pannier-GAL4 and UAS-DREFIR resulted in a split thorax phenotype. Monitoring of JNK activity in the wing disc by LacZ expression in a puckered (puc)-LacZ enhancer trap line revealed the reduction in DREF knockdown clones. These findings indicate that DREF is involved in regulation of Drosophila thorax development via actions on the JNK pathway., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Prosthetic patches are widely used for congenital diaphragmatic hernia (CDH) repair. We compared the complication rate of absorbable (Surgisis [SIS]; Cook Biotech, Inc, West Lafayette, IN) and nonabsorbable (polytetrafluoroethylene [PTFE]) materials for this purpose., Methods: This is a retrospective review of all neonates with CDH undergoing patch closure at our institution over 10 years. Meta-analysis was also performed combining our data with the published literature examining the effect of patch type on recurrence and small bowel obstruction (SBO)., Results: Primary patch (13 SIS, 9 PTFE) repair was performed in 22 (26%) of 84 patients with CDH. Groups were comparable in terms of demographics, hospital stay, ventilator days, need for high frequency oscillation, age at surgery, and length of follow-up. Likewise, recurrence rate (SIS, 4 [31%]; PTFE, 3 [33%]; P, nonsignificant [NS]), incidence of postoperative SBO (SIS, 1 [7%] vs PTFE, 2 [22%]; P, NS), and mortality (SIS, 2 [15%] and PTFE, 2 [22%]; P, NS) were similar. Meta-analysis failed to find a significant difference between SIS and PTFE both for recurrence rate (odds ratio, 1.21 [0.51-2.84]; P, NS) and SBO (odds ratio, 1.47 [0.44-4.96]; P, NS)., Conclusions: There was no difference in the incidence of CDH recurrence, SBO, or mortality post-CDH patch repair using either SIS or PTFE in our series. Meta-analysis failed to show any difference in recurrence and SBO rates between the 2 materials., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Pekin Duck is world-famous for its fast growth, but its breast muscle development is later and breast muscle content is lower compared with other muscular ducks. Therefore, it is very important to discover the genetic mechanism between breast muscle development and relative gene expression in Pekin duck. In current study, the genes which have relationships with breast muscle development were identified by suppression subtractive hybridization. A total of 403 positive clones were sequenced and 257 unigenes were obtained. The expression of 23 genes were analyzed in the breast muscle of 2-, 4-, 6-, 8- week old Pekin ducks. The results showed that unknown clone A233, C83 and C99 showed descending tendency as age increased; KBTBD10, HSPA8, MYL1, ZFP622, MARCH4, Nexilin, FABP4 and MUSTN1 had high expression levels at 6 weeks old; WAC, NT5C3, HSP90AA1, MRPL33, KLF6, TSNAX, CDC42EP3, HSPA4, TRAK1, NR2F2, HAUS1 and IGF1 had high expression levels at 8 weeks and showed ascending tendency as age increased. Expression of these 23 genes were also analyzed in breast muscle, leg muscle, heart, kidney, liver, muscular stomach and sebum cutaneum in 4-8-week old Pekin duck and results showed that most of these genes had high expression in breast muscle, leg muscle and heart.

During animal development, several planar cell polarity (PCP) pathways control tissue shape by coordinating collective cell behavior. Here, we characterize by means of multiscale imaging epithelium morphogenesis in the Drosophila dorsal thorax and show how the Fat/Dachsous/Four-jointed PCP pathway controls morphogenesis. We found that the proto-cadherin Dachsous is polarized within a domain of its tissue-wide expression gradient. Furthermore, Dachsous polarizes the myosin Dachs, which in turn promotes anisotropy of junction tension. By combining physical modeling with quantitative image analyses, we determined that this tension anisotropy defines the pattern of local tissue contraction that contributes to shaping the epithelium mainly via oriented cell rearrangements. Our results establish how tissue planar polarization coordinates the local changes of cell mechanical properties to control tissue morphogenesis.

Background: Early-onset scoliosis, when left untreated, leads to severe deformity. Until the last decade, treatment of progressive curves in young children often consisted of definitive spinal fusion. The recognition of thoracic insufficiency syndrome associated with definitive early fusion has led to the development of new surgical techniques developed to preserve spinal and thoracic growth in young patients with progressive scoliosis., Questions/purposes: We asked: (1) Does early definitive fusion arrest progression of spinal deformity? To what extent does early definitive spinal fusion influence (2) pulmonary function and (3) thoracic growth?, Methods: A Medline search of the published literature on early-onset scoliosis, congenital scoliosis, and infantile scoliosis between 2008 and 2010 was performed on spinal fusion for early-onset scoliosis, focusing on studies reporting pulmonary function at followup., Results: Spinal deformity is apparently not well controlled by early fusion since revision surgery has been required in 24% to 39% of patients who underwent presumed definitive fusion in early childhood. Restrictive pulmonary disease, defined as forced vital capacity less than 50% of normal, occurs in 43% to 64% of patients who undergo early fusion surgery with those children who have extensive thoracic fusions and whose fusions involve the proximal thoracic spine at highest risk. Thoracic growth after early surgery is an average of 50% of that seen in children with scoliosis who do not have early surgery. Diminished thoracic spinal height correlates with decreased forced vital capacity., Conclusions: The literature does not support routine definitive fusion of thoracic spinal deformity at an early age in children with scoliosis.

Background: Spine and chest wall deformities in children with early onset scoliosis (EOS) frequently impair respiratory function and postnatal growth of the lung. While a relationship between deformity and such impairment has been reported in children with adolescent idiopathic scoliosis it is not well understood in children with early-onset scoliosis (EOS)., Questions/purposes: We therefore describe (1) the preoperative relation between Cobb angle and forced vital capacity (FVC) in infants with EOS; (2) how changes in Cobb angle before and after surgery relate to changes in lung ventilation and perfusion in the right and left lungs., Methods: We measured FVC in 10 children with EOS < 3 years old using the raised volume rapid thoracic compression (RVRTC) technique and correlated them with Cobb angles. We then measured right lung contributions to total lung ventilation and perfusion using lung scans before and 4 to 57 months after placement of vertical expandable prosthetic titanium ribs (VEPTRs) in 15 children with EOS and correlated changes in right lung function with postoperative changes in Cobb angles., Results: In children 4 to 57 months of age, preoperative FVC (mean value, 83%; range, 63%-109% of predicted values) did not correlate with Cobb angles (mean value, 56º; range, 14°-120º). In children 1.8 to 11.5 years old, right lung ventilation and perfusion were abnormal in eight and seven children, respectively, but neither ventilation nor perfusion predictably normalized despite reductions in Cobb angle postoperatively., Conclusions: The data extend the age range of children with EOS whose Cobb angles correlate poorly with FVC preoperatively. The data are also consistent with reports that reduced Cobb angles after VEPTR insertion do not correlate with postoperative changes in respiratory function.

Thorax closure in Drosophila is a process during adult morphogenesis in which the anterior ends of the presumptive notum of the two wing imaginal discs fuse to make a seamless thorax. Similar to dorsal closure during embryogenesis, this process is regulated by plegic and JNK signaling pathways. Despite the fact that Peripodial Membrane (PM) cells do not contribute to the formation of any adult structure, they are known to facilitate the process of thorax closure. Here we show that JNK signaling is activated only in a subset of PM cells, known as medial edge cells. While the mechanism that activates JNK signaling specifically in the medial edge cells of the PM is still not understood, the results presented here show that the pair rule gene odd skipped is required to ensure that JNK signaling is not activated anywhere else in the wing disc. Medial edge cells of the PM are elongated in shape, while the remaining PM cells are hexagonal. Down regulation of JNK signaling in the medial edge cells results in defective thorax closure in adult flies. It also causes the transformation of the morphology of medial edge cells into hexagonal shape. Conversely, activation of JNK signaling in hexagonal cells of the PM causes transformation of their morphology to elongated shape. Thus, similar to dorsal closure during embryogenesis, JNK-mediated elongation of medial edge cells is functionally correlated to the process of thorax closure.

Because placental polychlorinated dibenzo-p-dioxins,dibenzofurans (PCDD/Fs) levels are associated with decreased free thyroxine (FT(4)) and thyroid stimulating hormone (TSH) in neonates, we assessed development by gender and maternal PCDD/Fs exposure at years 2 and 5 in 92 mother and newborn pairs. RIA quantified thyroid, sex, and growth hormones. Of 200 subjects followed up from November 2000, 136 and 149 were observed at year 2 and year 5,respectively. PCDD/Fs exposure levels were low (n = 35) or high (n = 35) in 70 subjects at year 2, low (n = 21) or high (n = 20) in 41 at year 5. Height, weight, BMI, and head circumference were significantly higher in males, chest girth significantly higher in females at year 2. Significantly, more girls had higher bone age (BA) and chronological age (CA) at both times. Height, weight, FT(4) x TSH, and transthyretin(TTR) at year 2; and height, triiodothyronine, and IGF-1 at year 5 differed significantly by PCDD/Fs level. In females, height, weight, CA,BA, and thyroid hormones differed significantly at year 2. In males, FT(4) x TSH at year 2 and IGF-1 at year 5 were significantly higher in the high PCDD/Fs group. In utero exposure to PCDD/Fs differentially affects growth and hormone levels in male and female preschool children.

Treating very young children with spinal deformities is challenging and complex, and it entails risks. The consequences of surgical treatment can be profound, with lifelong implications. The recent focus on "fusionless" surgery and spinal column lengthening strategies, such as growing rod instrumentation and the use of a Vertical Expandable Prosthetic Titanium Rib, illustrate the current understanding of the importance of spinal growth and lung development in infants and young children.

Background: During the development of the central nervous system (CNS) of Drosophila, neuronal stem cells, the neuroblasts (NBs), first generate a set of highly diverse neurons, the primary neurons that mature to control larval behavior, and then more homogeneous sets of neurons that show delayed maturation and are primarily used in the adult. These latter, 'secondary' neurons show a complex pattern of expression of broad, which encodes a transcription factor usually associated with metamorphosis, where it acts as a key regulator in the transitions from larva and pupa., Results: The Broad-Z3 (Br-Z3) isoform appears transiently in most central neurons during embryogenesis, but persists in a subset of these cells through most of larval growth. Some of the latter are embryonic-born secondary neurons, whose development is arrested until the start of metamorphosis. However, the vast bulk of the secondary neurons are generated during larval growth and bromodeoxyuridine incorporation shows that they begin expressing Br-Z3 about 7 hours after their birth, approximately the time that they have finished outgrowth to their initial targets. By the start of metamorphosis, the oldest secondary neurons have turned off Br-Z3 expression, while the remainder, with the exception of the very youngest, maintain Br-Z3 while they are interacting with potential partners in preparation for neurite elaboration. That Br-Z3 may be involved in early sprouting is suggested by ectopically expressing this isoform in remodeling primary neurons, which do not normally express Br-Z3. These cells now sprout into ectopic locations. The expression of Br-Z3 is transient and seen in all interneurons, but two other isoforms, Br-Z4 and Br-Z1, show a more selective expression. Analysis of MARCM clones shows that the Br-Z4 isoform is expressed by neurons in virtually all lineages, but only in those cells born during a window during the transition from the second to the third larval instar. Br-Z4 expression is then maintained in this temporal cohort of cells into the adult., Conclusion: These data show the potential for diverse functions of Broad within the developing CNS. The Br-Z3 isoform appears in all interneurons, but not motoneurons, when they first begin to interact with potential targets. Its function during this early sorting phase needs to be defined. Two other Broad isoforms, by contrast, are stably expressed in cohorts of neurons in all lineages and are the first examples of persisting molecular 'time-stamps' for Drosophila postembryonic neurons.

The BTB domain is a highly conserved protein-protein interaction motif and functions in diverse cellular processes, including transcriptional regulation, ion channel assembly, cytoskeleton dynamics and apoptosis. Recently, it was reported that some BTB domain-containing proteins associate with Cullin-3 (Cul3), an E3 ubiquitin ligase, and act as an adaptor for Cul3 recognition of its substrate. However, the target substrates for the Cul3/BTB protein E3 ubiquitin ligase complex are largely unknown. Here, we report the characterization of a novel Drosophila BTB protein, dKLHL18/CG3571. By purification of a dKLHL18-associated complex, we identified CG10324, CG5808, l(2)37Cb and dCul3/guftagu. Indeed, the physical association of dKLHL18 with these proteins was observed in insect S2 cells, and genetic interactions among the identified factors were also observed in thorax development. Moreover, transient overexpression of dKLHL18 increased the ubiquitinated protein levels of CG10324 and CG5808. These findings suggest that dKLHL18 is an adaptor for a dCul3 E3 ubiquitin ligase to accommodate CG10324, CG5808 and l(2)37Cb proteins for ubiquitination.

Study Design: Review of relevant literature including personal opinions., Objective: To review the current researches investigating the efficacy of growing rod and thoracic expansion techniques in the treatment of congenital spine deformity of young children, and to highlight the contrasting advantages and limitations in the fusionless treatment of progressive congenital scoliosis., Summary of Background Data: Congenital scoliosis has the potential for severe spinal deformity and thoracic insufficiency syndrome (TIS). Conventional fusion treatments in children tend to shorten the spine further exacerbating trunk shortening and TIS. In the surgical treatment of congenital spinal deformities in young children, while reconstructing the spinal deformity, one should simultaneously pursue preserving the growth potential of the vertebrae, improving the volume, symmetry, and functions of the thorax, and protecting this improvement during the growth. Today, employed in the treatment of spinal deformities of young children, there are 2 deformity reconstruction methods serving these targets: Growing rod technique and vertical expandable prosthetic titanium rib (VEPTR) with or without expansion thoracostomy., Methods: Peer-reviewed research articles and major international meeting presentations were reviewed. Methods were compared in terms of advantages and limitations., Results: The growing rod technique is a safe and reliable method in the treatment of congenital spine deformity of young children who present some flexibility in the anomalous segment, or when the congenital anomaly involves a vertebral segment too long for resection, or with compensating curve with structural pattern concomitant to the congenital deformity. Expansion thoracostomy and VEPTR are the appropriate choice for severe congenital spine deformity when a large amount of growth remains. Although ventilator dependence is significantly decreasing, thoracic volume and space available for the lung are increased after expansion thoracostomy and VEPTR., Conclusion: Growing rod technique should be used in patients where the primary problem is at the vertebral column. If the patient has rib fusions and/or TIS has developed, in other words, if the primary problem involves the thoracic cage, expansion thoracostomy and VEPTR should be an appropriate option.

Purpose of the Study: The purpose of this study is to assess the consequences brought by selective dorsal arthrodesis of thoracic spine (T1-T6) to the growth of spine and thoracic volume in operated and sham-operated New Zealand White rabbits, between prepubertal age and the end of somatic growth, through the study of computerised tomography (CT) scans periodically carried out on them after arthrodesis surgery., Material and Methods: Nine female rabbits were subjected to surgery for selective dorsal arthrodesis of the upper thoracic spine and three were sham-operated. Surgery was performed at age nine weeks, before the onset of puberty. Two "C"-shaped titanium bars were placed beside the spinous processes of the thoracic vertebrae to obtain a selective posterior arthrodesis of the first six thoracic vertebrae. Under general anesthesia, three CT scans were performed, 10 (t1), 55 (t2) and 139 (t3) days after surgery. Measures were obtained by Myrian Pro software for three different groups: group 1 with complete fusion, group 2 with incomplete fusion, group 3 sham-operated., Results: The total dorsal and ventral lengths of thoracic vertebral bodies in the spinal segment T1-T6 was smaller in group 1 and group 2 than in group 3, whereas no differences were observed between the three groups in the T7-T12 segment. The average of the dorsoventral/laterolateral thoracic diameter ratio at fused levels was less than 1 in group 1 as well as in group 2; on the contrary, in group 3 it was greater than 1. The sternum and lung volume grow less., Conclusions: Vertebral arthrodesis in the treatment of progressive idiopathic scoliosis in prepubertal patients is not ideal, but is still a choice in treating major deformities of the spine. Postoperative assessment of spinal deformity is essential, feasible and recordable through CT scans. Dorsal arthrodesis in prepubertal rabbits changes thoracic growth patterns. In operated rabbits, the dorsoventral thoracic diameter grows more slowly than the laterolateral thoracic diameter. The sternum, the total lengths of thoracic vertebral bodies in the spinal segment T1-T6 and lungs grow less. The Crankshaft phenomenon is evident at the fused vertebral levels where there is a reduction of thoracic kyphosis.

The Drosophila LIM-only (LMO) protein DLMO functions as a negative regulator of transcription during development of the fly wing. Here we report a novel role of DLMO as a positive regulator of transcription during the development of thoracic sensory bristles. We isolated new dlmo mutants, which lack some thoracic dorsocentral (DC) bristles. This phenotype is typical of malfunction of a thoracic multiprotein transcription complex, composed of CHIP, PANNIER (PNR), ACHAETE (AC), and DAUGHTERLESS (DA). Genetic interactions reveal that dlmo synergizes with pnr and ac to promote the development of thoracic DC bristles. Moreover, loss-of-function of dlmo reduces the expression of a reporter target gene of this complex in vivo. Using the GAL4-UAS system we also show that dlmo is spatially expressed where this complex is known to be active. Glutathione-S-transferase (GST)-pulldown assays showed that DLMO can physically bind CHIP and PNR through either of the two LIM domains of DLMO, suggesting that DLMO might function as part of this transcription complex in vivo. We propose that DLMO exerts its positive effect on DC bristle development by serving as a bridging molecule between components of the thoracic transcription complex.