Facilitative parenting and children's social, emotional and behavioural adjustment

Facilitative parenting (FP) supports the development of children’s social and emotional competence and effective peer relationships. Previous research has shown that FP discriminates between children bullied by peers from children who are not bullied, according to reports of teachers. This study investigates the association between FP and children’s social, emotional and behavioral problems, over and above the association with dysfunctional parenting (DP). 215 parents of children aged 5–11 years completed questionnaires about parenting and child behavior, and children and teachers completed measures of child bullying victimization. As predicted, FP accounted for variance in teacher reports of children’s bullying victimization as well as parent reports of children’s social and emotional problems and prosocial behavior better than that accounted for by DP. However for children’s reports of peer victimization the whole-scale DP was a better predictor than FP. Contrary to predictions, FP accounted for variance in conduct problems and hyperactivity better than DP. When analyses were replicated substituting subscales of dysfunctional and FP, a sub-set of FP subscales including Warmth, Supports Friendships, Not Conflicting, Child Communicates and Coaches were correlated with low levels of problems on a broad range of children’s adjustment problems. Parent–child conflict accounted for unique variance in children’s peer victimization (teacher report), peer problems, depression, emotional problems, conduct problems and hyperactivity. The potential relevance of FP as a protective factor for children against a wide range of adjustment problems is discussed

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

An Emerging Role for Epigenetics in Cerebral Palsy

Cerebral palsy is a set of common, severe, motor disabilities categorized by a static, nondegenerative encephalopathy arising in the developing brain and associated with deficits in movement, posture, and activity. Spastic CP, which is the most common type, involves high muscle tone and is associated with altered muscle function including poor muscle growth and contracture, increased extracellular matrix deposition, microanatomic disruption, musculoskeletal deformities, weakness, and difficult movement control. These muscle-related manifestations of CP are major causes of progressive debilitation and frequently require intensive surgical and therapeutic intervention to control. Current clinical approaches involve sophisticated consideration of biomechanics, radiologic assessments, and movement analyses, but outcomes remain difficult to predict. There is a need for more precise and personalized approaches involving omics technologies, data science, and advanced analytics. An improved understanding of muscle involvement in spastic CP is needed. Unfortunately, the fundamental mechanisms and molecular pathways contributing to altered muscle function in spastic CP are only partially understood. In this review, we outline evidence supporting the emerging hypothesis that epigenetic phenomena play significant roles in musculoskeletal manifestations of CP

DNA Methylation Analysis Reveals Distinct Patterns in Satellite Cell–Derived Myogenic Progenitor Cells of Subjects with Spastic Cerebral Palsy

Spastic type cerebral palsy (CP) is a complex neuromuscular disorder that involves altered skeletal muscle microanatomy and growth, but little is known about the mechanisms contributing to muscle pathophysiology and dysfunction. Traditional genomic approaches have provided limited insight regarding disease onset and severity, but recent epigenomic studies indicate that DNA methylation patterns can be altered in CP. Here, we examined whether a diagnosis of spastic CP is associated with intrinsic DNA methylation differences in myoblasts and myotubes derived from muscle resident stem cell populations (satellite cells; SCs). Twelve subjects were enrolled (6 CP; 6 control) with informed consent/assent. Skeletal muscle biopsies were obtained during orthopedic surgeries, and SCs were isolated and cultured to establish patient–specific myoblast cell lines capable of proliferation and differentiation in culture. DNA methylation analyses indicated significant differences at 525 individual CpG sites in proliferating SC–derived myoblasts (MB) and 1774 CpG sites in differentiating SC–derived myotubes (MT). Of these, 79 CpG sites were common in both culture types. The distribution of differentially methylated 1 Mbp chromosomal segments indicated distinct regional hypo– and hyper–methylation patterns, and significant enrichment of differentially methylated sites on chromosomes 12, 13, 14, 15, 18, and 20. Average methylation load across 2000 bp regions flanking transcriptional start sites was significantly different in 3 genes in MBs, and 10 genes in MTs. SC derived MBs isolated from study participants with spastic CP exhibited fundamental differences in DNA methylation compared to controls at multiple levels of organization that may reveal new targets for studies of mechanisms contributing to muscle dysregulation in spastic CP

Disruption of Basal Lamina Components in Neuromotor Synapses of Children with Spastic Quadriplegic Cerebral Palsy

<div><p>Cerebral palsy (CP) is a static encephalopathy occurring when a lesion to the developing brain results in disordered movement and posture. Patients present with sometimes overlapping spastic, athetoid/dyskinetic, and ataxic symptoms. Spastic CP, which is characterized by stiff muscles, weakness, and poor motor control, accounts for ∼80% of cases. The detailed mechanisms leading to disordered movement in spastic CP are not completely understood, but clinical experience and recent studies suggest involvement of peripheral motor synapses. For example, it is recognized that CP patients have altered sensitivities to drugs that target neuromuscular junctions (NMJs), and protein localization studies suggest that NMJ microanatomy is disrupted in CP. Since CP originates during maturation, we hypothesized that NMJ disruption in spastic CP is associated with retention of an immature neuromotor phenotype later in life. Scoliosis patients with spastic CP or idiopathic disease were enrolled in a prospective, partially-blinded study to evaluate NMJ organization and neuromotor maturation. The localization of synaptic acetylcholine esterase (AChE) relative to postsynaptic acetylcholine receptor (AChR), synaptic laminin β2, and presynaptic vesicle protein 2 (SV2) appeared mismatched in the CP samples; whereas, no significant disruption was found between AChR and SV2. These data suggest that pre- and postsynaptic NMJ components in CP children were appropriately distributed even though AChE and laminin β2 within the synaptic basal lamina appeared disrupted. Follow up electron microscopy indicated that NMJs from CP patients appeared generally mature and similar to controls with some differences present, including deeper postsynaptic folds and reduced presynaptic mitochondria. Analysis of maturational markers, including myosin, syntrophin, myogenin, and AChR subunit expression, and telomere lengths, all indicated similar levels of motor maturation in the two groups. Thus, NMJ disruption in CP was found to principally involve components of the synaptic basal lamina and subtle ultra-structural modifications but appeared unrelated to neuromotor maturational status.</p></div

CP NMJs have a reduced mitochondrial load.

<p>A) Confocal images showing double staining for acetylcholine receptor by α-bungarotoxin (red) and mitochondria (green) using a mouse monoclonal antibody for complex VI subunit I of cytochrome c oxidase (Mitosciences, Oregon). Images represent the mean intensities of fluorescence signal across 10 z-stacked images by confocal microscopy. CP NMJs show a decreased intensity for synaptic mitochondria. B) Average mitochondrial fluorescence intensities of NMJs of CP (93.25±8.017 SEM, n = 25 NMJs) and control (156.70±12.035 SEM, n = 25 NMJs) samples. Bars represent the mean ± SEM of immunofluorescence intensity in arbitrary fluorescence units based on the signal from the mitochondrial stain at the NMJs of CP and control samples.</p

NMJs from CP Patients by Electron Microscopy.

<p>A) Top panel shows an electron micrograph of a CP NMJ. A zoomed out image is shown in the upper right corner with a red line marking a Schwann cell nucleus, cyan marking the Schwann cell membrane, magenta marking the nerve terminal, yellow marking the postsynaptic folds, and green marking the postsynaptic nucleus. Scale bars = 1 µm. B) A zoomed image of primary folds in the CP NMJ is also shown. The blue lines indicate the general depth of postsynaptic fold penetrance into the muscle. For data analysis, each fold was measured separately using ImageJ software to draw trace lines for individual folds following the methods outlined by Banks et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070288#pone.0070288-Banks1" target="_blank">[27]</a>. C) A CP NMJ with a single mitochondrion in the nerve terminal (arrow). The total area occupied by mitochondria was calculated with ImageJ software by tracing each mitochondrion segment and measuring the summed mitochondrial area relative to the total area of the terminal.</p

Determination of appositional score.

<p>Sample images are shown for a single NMJ from a <i>spinalis</i> biopsy of a child with CP. The distribution of AChR (Panel A), AChE (B), and the composite image of both AChR and AChE (C) are shown. Each image was thresholded using the standard algorithm provided in the Image Pro Software, which objectively identifies foreground versus background pixels based on the distribution of intensities in the image, resulting in images D, E, and F. Distinct boundaries were reproducibly identifiable relative to background using this approach. A line drawn through the NMJ (G) provided the corresponding histogram (H) which displayed the intensities of AChR and AChE staining across the NMJ. The pixels above the preset threshold levels were categorized and counted to determine appositional scores.</p

Comparison of individual CP patients with the idiopathic scoliosis group.

<p>Pair-wise Mann-Whitney tests were run to determine how individual CP patients compared to the idiopathic scoliosis groups. R = AChR; O = outside of; E = AChE; L = laminin β2; V = SV2. +++ indicates that the child had significantly higher values than the control group, while −−− indicates that the child had significantly lower values than the control group (p≤0.002; note that this level of significance was selected because there were 25 CP children compared to the control/IS group).</p