Vitamin B-12 deficiency stimulates osteoclastogenesis via increased homocysteine and methylmalonic acid

The risk of nutrient deficiencies increases with age in our modern Western society, and vitamin B(12) deficiency is especially prevalent in the elderly and causes increased homocysteine (Hcy) and methylmalonic acid (MMA) levels. These three factors have been recognized as risk factors for reduced bone mineral density and increased fracture risk, though mechanistic evidence is still lacking. In the present study, we investigated the influence of B(12), Hcy, and MMA on differentiation and activity of bone cells. B(12) deficiency did not affect the onset of osteoblast differentiation, maturation, matrix mineralization, or adipocyte differentiation from human mesenchymal stem cells (hMSCs). B(12) deficiency caused an increase in the secretion of Hcy and MMA into the culture medium by osteoblasts, but Hcy and MMA appeared to have no effect on hMSC osteoblast differentiation. We further studied the effect of B(12), Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts from mouse bone marrow. We observed that B(12) did not show an effect on osteoclastogenesis. However, Hcy as well as MMA were found to induce osteoclastogenesis in a dose-dependent manner. On the basis of these results, we conclude that B(12) deficiency may lead to decreased bone mass by increased osteoclast formation due to increased MMA and Hcy levels

The nature of pre-­‐service science teachers’ argumentation in inquiry-­‐oriented laboratory context

The aim of this study was to investigate the kinds of argumentation schemes generated by pre-service elementary science teachers (PSTs) as they perform inquiry-oriented laboratory tasks, and to explore how argumentation schemes vary by task as well as by experimentation and discussion sessions. The model of argumentative and scientific inquiry was used as a design framework in the present study. According to the model, the inquiry of scientific topics was employed by groups of participants through experimentation and critical discussion sessions. The participants of the study were 35 PSTs, who teach middle school science to sixth through eighth grade students after graduation. The data were collected through video- and audio-recordings of the discussions made by PSTs in six inquiry-oriented laboratory sessions. For the analysis of data, pre-determined argumentation schemes by Walton were employed. The results illustrated that PSTs applied varied premises rather than only observations or reliable sources to ground their claims or to argue for a case or an action. It is also worthy of notice that the construction and evaluation of scientific knowledge claims resulted in different numbers and kinds of arguments. Results of this study suggest that designing inquiry-oriented laboratory environments, which are enriched with critical discussion, provides discourse opportunities that can support argumentation. Moreover, PSTs can be encouraged to support and promote argumentation in their future science classrooms if they engage in argumentation integrated instructional strategies

Penalties through XPM crosstalk in a switched long haul standard fiber WDM system based on normalized transmission sections

For the first time penalties due to XPM crosstalk have been measured by switching neighbouring channels in a long distance 16*10 Gb/s ASK NRZ system based on standard single mode fibre (SMF) links with dispersion optimized transmission sections

Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration

Ubiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific deubiquitinating enzyme, is one of the most abundant proteins in the brain. We describe three siblings from a consanguineous union with a previously unreported early-onset progressive neurodegenerative syndrome featuring childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfuction, and spasticity with upper motor neuron dysfunction. Through homozygosity mapping of the affected individuals followed by whole-exome sequencing of the index case, we identified a previously undescribed homozygous missense mutation within the ubiquitin binding domain of UCHL1 (UCHL1(GLU7ALA).), shared by all affected subjects. As demonstrated by isothermal titration calorimetry, purified UCHL1(GLU7ALA), compared with WT, exhibited at least sevenfold reduced affinity for ubiquitin. In vitro, the mutation led to a near complete loss of UCHL1 hydrolase activity. The GLU7ALA variant is predicted to interfere with the substrate binding by restricting the proper positioning of the substrate for tunneling underneath the cross-over loop spanning the catalytic cleft of UCHL1. This interference with substrate binding, combined with near complete loss of hydrolase activity, resulted in a >100-fold reduction in the efficiency of UCHL1(GLU7ALA) relative to WT. These findings demonstrate a broad requirement of UCHL1 in the maintenance of the nervous system