Hypophosphatasia: A Systemic Skeletal Disorder Caused by Alkaline Phosphatase Deficiency

Hypophosphatasia (HPP) is an inherited systemic bone disease caused by the deficiency of tissue-nonspecific alkaline phosphatase (TNAP). HPP is classified into six forms and the symptoms of HPP vary depending on the form. The pathophysiology of HPP is basically due to a defect of bone mineralization. TNAP is encoded by the ALPL gene, and the TNAP protein expressed in bone, kidney, liver, and neuronal cells and is linked to the cell membrane via a glycosylphosphatidylinositol anchor. TNAP is an ectoenzyme hydrolyzing phosphate compound such as inorganic pyrophosphate. TNAP plays an important role in mineralization of hard tissues. Defect of mineralization process causes hypomineralization of hard tissues, which leads to rickets or osteomalacia and dental manifestations. In addition, hypomineralization of the ribs results in respiratory failure in the severe forms, which is the main cause of death. Inheritance of HPP is autosomal recessive, but autosomal dominant cases have been reported in the milder forms. To date, a total of 335 mutations in the ALPL gene have been reported, and mutation sites are scattered throughout the gene. Recent development of enzyme replacement therapy has opened up a new vista on the treatment of this previously untreatable disease

Nutrition education in medical schools in Japan: results from a questionnaire survey

Diet is known to play a critical role in the pathogenesis of major age-related chronic diseases, which are rapidly becoming more common in Japan and other industrialized countries. However, traditional medical education has not provided adequate knowledge of nutrition. To understand the current status of nutrition education in Japan, we sent a questionnaire to all Japanese medical schools to survey their nutrition curricula. The questionnaire was sent to 79 medical schools in Japan, which includes all medical schools except for that of the authors. We also used a questionnaire to survey second year medical students just after they received a short nutrition course at Nippon Medical School. Fifty-seven medical schools (72.2%) responded to the questionnaire: 12 (21.1% of the responding schools) offered a "nutrition" course and 3 (5.4%) offered a "clinical nutrition" course. Including "nutrition" and "clinical nutrition" courses, 14 of the responding medical schools (24. 6 %) offered stand-alone nutrition courses in their undergraduate education. Although a total of 48 of the responding medical schools (84.2%) offered some nutrition topics, only 8 of the responding schools (14.0%) may have offered substantial nutrition education. No special postgraduate course in medical or clinical nutrition was offered by any of the schools. Despite this, more than 80% of the students that appeared to be interested in a nutrition course recognized the importance of nutrition education in medical school. This survey showed that nutrition education in Japanese medical schools remains inadequate and changes are necessary

Transcriptome analyses of mouse and human mammary cell subpopulations reveal multiple conserved genes and pathways

INTRODUCTION: Molecular characterization of the normal epithelial cell types that reside in the mammary gland is an important step toward understanding pathways that regulate self-renewal, lineage commitment, and differentiation along the hierarchy. Here we determined the gene expression signatures of four distinct subpopulations isolated from the mouse mammary gland. The epithelial cell signatures were used to interrogate mouse models of mammary tumorigenesis and to compare with their normal human counterpart subsets to identify conserved genes and networks. METHODS: RNA was prepared from freshly sorted mouse mammary cell subpopulations (mammary stem cell (MaSC)-enriched, committed luminal progenitor, mature luminal and stromal cell) and used for gene expression profiling analysis on the Illumina platform. Gene signatures were derived and compared with those previously reported for the analogous normal human mammary cell subpopulations. The mouse and human epithelial subset signatures were then subjected to Ingenuity Pathway Analysis (IPA) to identify conserved pathways. RESULTS: The four mouse mammary cell subpopulations exhibited distinct gene signatures. Comparison of these signatures with the molecular profiles of different mouse models of mammary tumorigenesis revealed that tumors arising in MMTV-Wnt-1 and p53-/- mice were enriched for MaSC-subset genes, whereas the gene profiles of MMTV-Neu and MMTV-PyMT tumors were most concordant with the luminal progenitor cell signature. Comparison of the mouse mammary epithelial cell signatures with their human counterparts revealed substantial conservation of genes, whereas IPA highlighted a number of conserved pathways in the three epithelial subsets. CONCLUSIONS: The conservation of genes and pathways across species further validates the use of the mouse as a model to study mammary gland development and highlights pathways that are likely to govern cell-fate decisions and differentiation. It is noteworthy that many of the conserved genes in the MaSC population have been considered as epithelial-mesenchymal transition (EMT) signature genes. Therefore, the expression of these genes in tumor cells may reflect basal epithelial cell characteristics and not necessarily cells that have undergone an EMT. Comparative analyses of normal mouse epithelial subsets with murine tumor models have implicated distinct cell types in contributing to tumorigenesis in the different models

Surface segregation at the aluminum interface of poly(3-hexylthiophene)/fullerene solar cells

The effects of thermal annealing before and after Al deposition on poly 3-hexylthiophene P3HT6, 6-phenyl-C61 butyric acid methyl ester PCBM blend solar cells were investigated by current density-voltage measurements and x-ray photoelectron spectroscopy XPS . Compared to the preannealed device, the postannealed device exhibited enhanced open-circuit voltage VOC, which is ascribed to the decrease in the reverse saturation current density J0. The XPS measurements demonstrated that P3HT is dominant at the Al interface in the preannealed device while PCBM is instead dominant in the postannealed device. This surface-segregated PCBM formed in the postannealed device can serve as a hole-blocking layer at the Al interface to reduce J0, and therefore improve VOC

Surface segregation at the aluminum interface of poly(3-hexylthiophene)/fullerene solar cells

The effects of thermal annealing before and after Al deposition on poly 3-hexylthiophene P3HT6, 6-phenyl-C61 butyric acid methyl ester PCBM blend solar cells were investigated by current density-voltage measurements and x-ray photoelectron spectroscopy XPS . Compared to the preannealed device, the postannealed device exhibited enhanced open-circuit voltage VOC, which is ascribed to the decrease in the reverse saturation current density J0. The XPS measurements demonstrated that P3HT is dominant at the Al interface in the preannealed device while PCBM is instead dominant in the postannealed device. This surface-segregated PCBM formed in the postannealed device can serve as a hole-blocking layer at the Al interface to reduce J0, and therefore improve VOC

Immunoproteomic identification of anti-C9 autoimmune antibody in patients with seronegative obstetric antiphospholipid syndrome

<div><p>Immunoproteomic analysis was performed to identify unknown, pathology-related molecules in patients with seronegative (SN) obstetric antiphospholipid syndrome (APS) who clinically satisfied the diagnostic criteria for APS, but not the serological criteria. We collected peripheral blood from 13 SN-APS outpatients with known thrombotic predisposition, 13 with no known thrombotic predisposition, and four multiparous women with no history of miscarriage (control). Plasma proteins from volunteers were purified and used as plasma protein antigens. Two-dimensional immunoblotting was performed using pooled control or SN-APS serum samples as the primary antibodies. Mass spectrometry of reactive spots specific to SN-APS serum led to the identification of complement molecule C9. Western blotting using commercial purified alkylated C9 was performed to detect autoantibodies. Examination of individual patient serum identified reactivity in one patient with, and in two patients without known thrombotic predisposition. This study suggests that SN-APS pathologies were associated with autoantibodies that react to specific C9 epitopes.</p></div