Mechanism for release of alkaline phosphatase caused by glycosylphosphatidylinositol deficiency in patients with hyperphosphatasia mental retardation syndrome

Hyperphosphatasia mental retardation syndrome (HPMR), an autosomal recessive disease characterized by mental retardation and elevated serum alkaline phosphatase (ALP) levels, is caused by mutations in the coding region of the phosphatidylinositol glycan anchor biosynthesis, class V (PIGV) gene, the product of which is a mannosyltransferase essential for glycosylphosphatidylinositol (GPI) biosynthesis. Mutations found in four families caused amino acid substitutions A341E, A341V, Q256K, and H385P, which drastically decreased expression of the PIGV protein. Hyperphosphatasia resulted from secretion of ALP, a GPI-anchored protein normally expressed on the cell surface, into serum due to PIGV deficiency. In contrast, a previously reported PIGM deficiency, in which there is a defect in the transfer of the first mannose, does not result in hyperphosphatasia. To provide insights into the mechanism of ALP secretion in HPMR patients, we took advantage of CHO cell mutants that are defective in various steps of GPI biosynthesis. Secretion of ALP requires GPI transamidase, which in normal cells, cleaves the C-terminal GPI attachment signal peptide and replaces it with GPI. The GPI-anchored protein was secreted substantially into medium from PIGV-, PIGB-, and PIGF-deficient CHO cells, in which incomplete GPI bearing mannose was accumulated. In contrast, ALP was degraded in PIGL-, DPM2-, or PIGX-deficient CHO cells, in which incomplete shorter GPIs that lacked mannose were accumulated. Our results suggest that GPI transamidase recognizes incomplete GPI bearing mannose and cleaves a hydrophobic signal peptide, resulting in secretion of soluble ALP. These results explain the molecular mechanism of hyperphosphatasia in HPMR.     

Blood flow to long bones indicates activity metabolism in mammals, reptiles and dinosaurs

The cross-sectional area of a nutrient foramen of a long bone is related to blood flow requirements of the internal bone cells that are essential for dynamic bone remodelling. Foramen area increases with body size in parallel among living mammals and non-varanid reptiles, but is significantly larger in mammals. An index of blood flow rate through the foramina is about 10 times higher in mammals than in reptiles, and even higher if differences in blood pressure are considered. The scaling of foramen size correlates well with maximum whole-body metabolic rate during exercise in mammals and reptiles, but less well with resting metabolic rate. This relates to the role of blood flow associated with bone remodelling during and following activity. Mammals and varanid lizards have much higher aerobic metabolic rates and exercise-induced bone remodelling than non-varanid reptiles. Foramen areas of 10 species of dinosaur from five taxonomic groups are generally larger than from mammals, indicating a routinely highly active and aerobic lifestyle. The simple measurement holds possibilities offers the possibility of assessing other groups of extinct and living vertebrates in relation to body size, behaviour and habitat.     

NHS-A isoform of the NHS gene is a novel interactor of ZO-1

Mutations in the NHS (Nance-Horan Syndrome) gene lead to severe congenital cataracts, dental defects and sometimes mental retardation. NHS encodes two protein isoforms, NHS-A and -1A that display cell-type dependent differential expression and localization. Here we demonstrate that of these two isoforms, the NHS-A isoform associates with the cell membrane in the presence of intercellular contacts and it immunoprecipitates with the tight junction protein ZO-1 in MDCK (Madin Darby Canine Kidney) epithelial cells and in neonatal rat lens. The NHS-1A isoform however is a cytoplasmic protein. Both Nhs isoforms are expressed during mouse development. Immunolabelling of developing mouse with the anti-NHS antibody that detects both isoforms revealed the protein in the developing head including the eye and brain. It was primarily expressed in epithelium including neural epithelium and certain vascular endothelium but only weakly expressed in mesenchymal cells. In the epithelium and vascular endothelium the protein associated with the cell membrane and co-localized with ZO-1, which indirectly indicates expression of the Nhs-A isoform in these structures. Membrane localization of the protein in the lens vesicle similarly supports Nhs-A expression. In conclusion, the NHS-A isoform of NHS is a novel interactor of ZO-1 and may have a role at tight junctions. This isoform is important in mammalian development especially of the organs in the head.     

海链藻(Thalassiosira)与圆筛藻(Coscinodiscus)的形态学比较研究

海链藻属（Thalassiosira）和圆筛藻属（Coscinodiscus）的种类繁多,是硅藻门中的大属和代表属。两者的形态学特征具有较多相似之处,易混淆鉴定。通过光学显微镜和电镜观察,比较研究了海链藻和圆筛藻种类的形态学特征。海链藻种类除了具有1~2个唇形突之外,还具有数量较多的支持突,少数种类具有闭合突;筛膜位于壳面内侧;中孔在壳面外侧。而圆筛藻种类只具有数量众多的唇形突,且其中两个较大;筛膜位于壳面外侧;中孔在壳面内侧。由于两属形态学特征的区别只有在电镜下才能清晰观察到,因此尚有较多的分类修订工作需要进行。     

Does the Segregation of Evolution in Biology Textbooks and Introductory Courses Reinforce Students’ Faulty Mental Models of Biology and Evolution?

The well-established finding that substantial confusion and misconceptions about evolution and natural selection persist after college instruction suggests that these courses neither foster accurate mental models of evolution’s mechanisms nor instill an appreciation of evolution’s centrality to an understanding of the living world. Our essay explores the roles that introductory biology courses and textbooks may play in reinforcing undergraduates’ pre-existing, faulty mental models of the place of evolution in the biological sciences. Our content analyses of the three best-selling introductory biology textbooks for majors revealed the conceptual segregation of evolutionary information. The vast majority of the evolutionary terms and concepts in each book were isolated in sections about evolution and diversity, while remarkably few were employed in other sections of the books. Standardizing the data by number of pages per unit did not alter this pattern. Students may fail to grasp that evolution is the unifying theme of biology because introductory courses and textbooks reinforce such isolation. Two goals are central to resolving this problem: the desegregation of evolution as separate “units” or chapters and the active integration of evolutionary concepts at all levels and across all domains of introductory biology.     

Salivary testosterone does not predict mental rotation performance in men or women

Multiple studies report relationships between circulating androgens and performance on sexually differentiated spatial cognitive tasks in human adults, yet other studies find no such relationships. Relatively small sample sizes are a likely source of some of these discrepancies. The present study thus tests for activational effects of testosterone (T) using a within-participants design by examining relationships between diurnal fluctuations in salivary T and performance on a male-biased spatial cognitive task (Mental Rotation Task) in the largest sample yet collected: 160 women and 177 men. T concentrations were unrelated to within-sex variation in mental rotation performance in both sexes. Further, between-session learning-related changes in performance were unrelated to T levels, and circadian changes in T were unrelated to changes in spatial performance in either sex. These results suggest that circulating T does not contribute substantially to sex differences in spatial ability in young men and women. By elimination, the contribution of androgens to sex differences in human performance on these tasks may be limited to earlier, organizational periods.     

农村留守孩心理健康的家庭因素研究

青少年时期是儿童个性发展的一个重要时期,个性发展有较大的可塑性。目前农村劳动力迁移导致了大批留守儿童亲子教育缺失和家庭教育缺位。本文对留守儿童心理健康的相关研究进行了整理,分析了影响留守儿童心理健康状况的四个主要家庭因素,并总结了关于为留守儿童建立社区学校和家庭的三维支持系统的建议。     

Screening for subtelomeric rearrangements using genetic markers in 70 patients with unexplained mental retardation

Cryptic unbalanced rearrangements involving chromosome ends are a significant cause of idiopathic mental retardation. The most frequently used technique to screen for these subtle rearrangements is Multiprobe fluorescence in situ hybridization (FISH). As this is a labor-intensive technique, we used microsatellite genotyping to detect possible subtelomeric rearrangements in a study population. Out of the 70 patients we screened, three chromosomal rearrangements were detected: a deletion of marker D2S2986, a deletion of marker D7S594 and a deletion of marker D19S424. However, none of these aberrations appeared to be disease causing.     

NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytoplasmic shuttling protein associated with active synaptoneurosomes

Fragile X syndrome, the most common cause of inherited mental retardation, is caused by the absence of FMRP (Fragile X Mental Retardation Protein). FMRP is an RNA binding protein reported to be involved in translational control, notably at postsynaptic sites of protein synthesis as a part of a multiprotein/mRNA complex. One of the FMRP interactors, NUFIP1, is an RNA binding protein with an expression profile matching that of FMRP. We now show that in the nucleus NUFIP1 is localized in the nuclear matrix in RNA-containing structures lying in the proximity of, but not overlapping with, sites of nascent RNA. NUFIP1 is also present in the cytoplasm, where it is associated with ribosomes, similarly to FMRP. In neurons NUFIP1 can be detected in functional synaptoneurosomes, colocalizing with ribosomes. Consistent with its subcellular localization in both nucleus and cytoplasm, we show that NUFIP1 contains a functional CRM1-dependent nuclear export signal and is able to shuttle between these two cellular compartments. These findings suggest the involvement of NUFIP1 in the export and localization of mRNA and, in association with FMRP, in the regulation of local protein synthesis near synapses.