A Polymorphism in a Gene Encoding Perilipin 4 Is Associated with Height but not with Bone Measures in Individuals from the Framingham Osteoporosis Study

There is increasing interest in identifying new pathways and candidate genes that confer susceptibility to osteoporosis. There is evidence that adipogenesis and osteogenesis may be related, including a common bone marrow progenitor cell for both adipocytes and osteoblasts. Perilipin 1 (PLIN1) and Perilipin 4 (PLIN4) are members of the PATS family of genes and are involved in lipolysis of intracellular lipid deposits. A previous study reported gender-specific associations between one polymorphism of PLIN1 and bone mineral density (BMD) in a Japanese population. We hypothesized that polymorphisms in PLIN1 and PLIN4 would be associated with bone measures in adult Caucasian participants of the Framingham Osteoporosis Study (FOS). We genotyped 1,206 male and 1,445 female participants of the FOS for four single-nucleotide polymorphism (SNPs) in PLIN1 and seven SNPs in PLIN4 and tested for associations with measures of BMD, bone ultrasound, hip geometry, and height. We found several gender-specific significant associations with the measured traits. The association of PLIN4 SNP rs8887, G>A with height in females trended toward significance after simulation testing (adjusted P = 0.07) and remained significant after simulation testing in the combined-sex model (adjusted P = 0.033). In a large study sample of men and women, we found a significant association between one SNP in PLIN4 and height but not with bone traits, suggesting that PATS family genes are not important in the regulation of bone. Identification of genes that influence human height may lead to a better understanding of the processes involved in growth and development

Development of the infant foot as a load bearing structure : study protocol for a longitudinal evaluation (the Small Steps study)

Background An improved understanding of the structural and functional development of the paediatric foot is fundamental to a strong theoretical framework for health professionals and scientists. An infant’s transition from sitting, through crawling and cruising, to walking is when the structures and function of the foot must adapt to bearing load. The adaptation of skin and other hard and soft tissue, and foot and gait biomechanics, during this time is poorly understood. This is because data characterising the foot tissue and loading pre-walking onset does not exist. Of the existing kinematic and plantar pressure data, few studies have collected data which reflects the real-life activities of infants with modern equipment. Methods This is a longitudinal study and part of the Great Foundations Initiative, a collaborative project between the University of Brighton and the University of Salford, which is seeking to improve foot health in children. Two cohorts of 50 infants will be recruited at the two sites (University of Brighton, Eastbourne, UK and University of Salford, Salford, UK). Infants will be recruited when they first reach for their feet and attend four laboratory visits at milestones related to foot loading, with experienced independent walking being the final milestone. Data collection will include tissue characteristics (skin thickness, texture, elasticity, pH and tendon thickness and cross-sectional area), plantar pressures and kinematics captured during real world locomotion tasks. Discussion This study will provide a database characterising the development of the infant foot as it becomes a weight bearing structure. The data will allow effective comparison and quantification of changes in structure and function due to maturation and loading by measuring pre and post established walking. Additional variables which impact on the development of the foot (gender, ethnicity and body weight) will also be factored into our analysis. This will help us to advance understanding of the determinants of foot development in early childhood

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Neurodevelopmental milestones and associated behaviours are similar among healthy children across diverse geographical locations.

It is unclear whether early child development is, like skeletal growth, similar across diverse regions with adequate health and nutrition. We prospectively assessed 1307 healthy, well-nourished 2-year-old children of educated mothers, enrolled in early pregnancy from urban areas without major socioeconomic or environmental constraints, in Brazil, India, Italy, Kenya and UK. We used a specially developed psychometric tool, WHO motor milestones and visual tests. Similarities across sites were measured using variance components analysis and standardised site differences (SSD). In 14 of the 16 domains, the percentage of total variance explained by between-site differences ranged from 1.3% (cognitive score) to 9.2% (behaviour score). Of the 80 SSD comparisons, only six were >±0.50 units of the pooled SD for the corresponding item. The sequence and timing of attainment of neurodevelopmental milestones and associated behaviours in early childhood are, therefore, likely innate and universal, as long as nutritional and health needs are met

Overlapping phenotypes in autism spectrum disorder and developmental coordination disorder: A cross-syndrome comparison of motor and social skills

Motor and social difficulties are often found in children with an autism spectrum disorder (ASD) and with developmental coordination disorder (DCD), to varying degrees. This study investigated the extent of overlap of these problems in children aged 7-10 years who had a diagnosis of either ASD or DCD, compared to typically-developing controls. Children completed motor and face processing assessments. Parents completed questionnaires concerning their child’s early motor and current motor and social skills. There was considerable overlap between the ASD and DCD groups on the motor and social assessments, with both groups more impaired than controls. Furthermore, motor skill predicted social functioning for both groups. Future research should consider the relationships between core symptoms and their consequences in other domains

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion