Osteoidosis leads to altered differentiation and function of osteoclasts

In patients with osteomalacia, a defect in bone mineralization leads to changed characteristics of the bone surface. Considering that the properties of the surrounding matrix influence function and differentiation of cells, we aimed to investigate the effect of osteoidosis on differentiation and function of osteoclasts. Based on osteomalacic bone biopsies, a model for osteoidosis in vitro (OIV) was established. Peripheral blood mononuclear cells were differentiated to osteoclasts on mineralized surfaces (MS) as internal control and on OIV. We observed a significantly reduced number of osteoclasts and surface resorption on OIV. Atomic force microscopy revealed a significant effect of the altered degree of mineralization on surface mechanics and an unmasking of collagen fibres on the surface. Indeed, coating of MS with RGD peptides mimicked the resorption phenotype observed in OIV, suggesting that the altered differentiation of osteoclasts on OIV might be associated with an interaction of the cells with amino acid sequences of unmasked extracellular matrix proteins containing RGD sequences. Transcriptome analysis uncovered a strong significant up-regulation of transmembrane glycoprotein TROP2 in osteoclastic cultures on OIV. TROP2 expression on OIV was also confirmed on the protein level and found on the bone surface of patients with osteomalacia. Taken together, our results show a direct influence of the mineralization state of the extracellular matrix surface on differentiation and function of osteoclasts on this surface which may be important for the pathophysiology of osteomalacia and other bone disorders with changed ratio of osteoid to bone

The identity of Stenorhabdium temporale Werner, 1909 (Serpentes: Colubroidea)

Re-examination of the type material of Ligonirostra Stuhlmanni Pfeffer, 1893 (original spelling, now Prosymna stuhlmanni) and comparison with the sole type specimen of its synonym Stenorhabdium temporale Werner, 1909 revealed a number of significant morphological differences between these taxa. Detailed analyses of pholidosis and osteology of comparative material show that S. temporale is in fact a subjective junior synonym of Pseudorabdion longiceps (Cantor, 1847). A lectotype and a paralectotype of Ligonirostra stuhlmanni are designated and described

Behavioral Versus Nonbehavioral Guided Self-Help for Parents of Children With Externalizing Disorders in a Randomized Controlled Trial

Self-help interventions for parents, which have a behavioral basis, are considered to be an effective treatment option for children with externalizing disorders. Nonbehavioral approaches are widely used but have little empirical evidence. The main objective of this trial was to compare the efficacy of a behavioral and a nonbehavioral guided self-help program for parents. Families of children (aged 4-11 years) diagnosed with attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) were randomized to either a behavioral or a nonbehavioral guided self-help program including 8 parenting booklets and 10 counseling telephone calls. The analyses considered the ratings of 5 informants: blinded clinician, therapist, participant, (her or his) partner, and teacher. Of the 149 families randomized to treatment (intention-to-treat sample [ITT]), 110 parents completed the intervention (per-protocol sample [PP]). For the 4 primary outcome measures (blinded clinician- and participant-rated ADHD and ODD) at post assessment, the analysis revealed a treatment advantage for the behavioral group in blinded clinician-rated ODD symptoms (ITT: d = 0.37; PP: d = 0.35). Further treatment differences, all in favor of the behavioral group (ITT and PP), were detected in therapist ratings (i.e., ODD) and participant ratings (e.g., parental self-efficacy [only PP], negative parenting behavior, parental stress). In both samples, no differences were found at post-assessment for ratings of the partner and the teacher, or at the 12-month follow-up (only participant ratings available). Behavioral guided self-help shows some treatment advantage in the short term. No superiority over nonbehavioral therapy was detected 12 months after treatment termination

Osteoidosis leads to altered differentiation and function of osteoclasts

In patients with osteomalacia, a defect in bone mineralization leads to changed characteristics of the bone surface. Considering that the properties of the surrounding matrix influence function and differentiation of cells, we aimed to investigate the effect of osteoidosis on differentiation and function of osteoclasts. Based on osteomalacic bone biopsies, a model for osteoidosis in vitro (OIV) was established. Peripheral blood mononuclear cells were differentiated to osteoclasts on mineralized surfaces (MS) as internal control and on OIV. We observed a significantly reduced number of osteoclasts and surface resorption on OIV. Atomic force microscopy revealed a significant effect of the altered degree of mineralization on surface mechanics and an unmasking of collagen fibres on the surface. Indeed, coating of MS with RGD peptides mimicked the resorption phenotype observed in OIV, suggesting that the altered differentiation of osteoclasts on OIV might be associated with an interaction of the cells with amino acid sequences of unmasked extracellular matrix proteins containing RGD sequences. Transcriptome analysis uncovered a strong significant up-regulation of transmembrane glycoprotein TROP2 in osteoclastic cultures on OIV. TROP2 expression on OIV was also confirmed on the protein level and found on the bone surface of patients with osteomalacia. Taken together, our results show a direct influence of the mineralization state of the extracellular matrix surface on differentiation and function of osteoclasts on this surface which may be important for the pathophysiology of osteomalacia and other bone disorders with changed ratio of osteoid to bone

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries