TULA-2, a novel histidine phosphatase, regulates bone remodeling by modulating osteoclast function

Bone is a dynamic tissue that depends on the intricate relationship between protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP) for maintaining homeostasis. PTKs and PTPs act like molecular on and off switches and help modulate differentiation and the attachment of osteoclasts to bone matrix regulating bone resorption. The protein T cell ubiquitin ligand-2 (TULA-2), which is abundantly expressed in osteoclasts, is a novel histidine phosphatase. Our results show that of the two family members, only TULA-2 is expressed in osteoclasts and that its expression is sustained throughout the course of osteoclast differentiation, suggesting that TULA-2 may play a role during early as well late stages of osteoclast differentiation. Skeletal analysis of mice that do not express TULA or TULA-2 proteins (DKO mice) revealed that there was a decrease in bone volume due to increased osteoclast numbers and function. Furthermore, in vitro experiments indicated that bone marrow precursor cells from DKO mice have an increased potential to form osteoclasts. At the molecular level, the absence of TULA-2 in osteoclasts results in increased Syk phosphorylation at the Y352 and Y525/526 residues and activation of phospholipase C gamma 2 (PLCγ2) upon engagement of immune-receptor-tyrosine-based-activation-motif (ITAM)—mediated signaling. Furthermore, expression of a phosphatase-dead TULA-2 leads to increased osteoclast function. Taken together, these results suggest that TULA-2 negatively regulates osteoclast differentiation and function.     

高成形性镁合金板材的成分优化

镁是最轻的金属结构材料。然而,镁合金板材具有织构强,室温成形性差的瓶颈难题,限制其广泛应用。虽然研究发现在Mg–Zn–Zr合金体系同添加钙或钆能弱化织构,提高成形性,但这两种元素添加后对的效果尚未有过系统比较和研究。本文旨在展现微合金添加钆和钙对于显微结构和力学性能的影响规律。本文发现,Mg–Zn–Gd–Zr 与 Mg–Zn–Ca–Zr轧板有类似的弱织构,但是Mg–Zn–Gd–Zr轧板的延伸率和成形性高于Mg–Zn–Ca–Zr。当在Mg–1Zn–0.5Zr合金中添加0.4wt%钆、0.2wt%钙时能获得最高的室温延伸率,其深冲成形性可以和铝合金板材6016相媲美。当钙的含量从0.2wt%提升至0.5wt%后,合金板材的延伸率与成形性下降,其主要原因是钙的过量添加导致了晶界脆化,降低了晶界韧性从而裂纹容易从晶界处萌生并扩展。     

Deliberative Inquiry: Integrated Ways of Working in Children Services

In striving for greater integration of children services across a number of government and non government agencies, this paper examines the effect of drawing on deliberative inquiry as the lever for realising greater alignment across agencies. The paper discusses the need for improvement in UK local government children??s services and then offers a review of the dialogue based inquiry approaches. In so doing, the paper highlights the Socratic mode of inquiry, emphasising the dual strategies of penetrative questioning, elenchus, and the process of founding new knowledge through working through confusion, aporia. This paper then reports how a London borough realised sustained change through the adoption of deliberative inquiry. The study achieved successful integration through the penetrating and contextually sensitive dialogue the inquiry participants generated, allowing them to develop the capability for realising effective organisational change. The paper concludes that deliberative inquiry facilitates individuals to speak their concerns in a manner that prompts ??consensually accepted beliefs?? to emerge through paying equal attention to the motivation of the inquiry participants, as well as to the reality of the contextual demands they need to confront.     

Sequencing and comparison of yeast species to identify genes and regulatory elements

Identifying the functional elements encoded in a genome is one of the principal challenges in modern biology. Comparative genomics should offer a powerful, general approach. Here, we present a comparative analysis of the yeast Saccharomyces cerevisiae based on high-quality draft sequences of three related species (S. paradoxus, S. mikatae and S. bayanus). We first aligned the genomes and characterized their evolution, defining the regions and mechanisms of change. We then developed methods for direct identification of genes and regulatory motifs. The gene analysis yielded a major revision to the yeast gene catalogue, affecting approximately 15% of all genes and reducing the total count by about 500 genes. The motif analysis automatically identified 72 genome-wide elements, including most known regulatory motifs and numerous new motifs. We inferred a putative function for most of these motifs, and provided insights into their combinatorial interactions. The results have implications for genome analysis of diverse organisms, including the human.     

Genome-wide atlas of gene expression in the adult mouse brain

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.