Intrinsic Promoter Activities of Primary DNA Sequences in the Human Genome

In order to understand an overview of promoter activities intrinsic to primary DNA sequences in the human genome within a particular cell type, we carried out systematic quantitative luciferase assays of DNA fragments corresponding to putative promoters for 472 human genes which are expressed in HEK (human embryonic kidney epithelial) 293 cells. We observed the promoter activities of them were distributed in a bimodal manner; putative promoters belonging to the first group (with strong promoter activities) were designated as P1 and the latter (with weak promoter activities) as P2. The frequencies of the TATA-boxes, the CpG islands, and the overall G + C-contents were significantly different between these two populations, indicating there are two separate groups of promoters. Interestingly, similar analysis using 251 randomly isolated genomic DNA fragments showed that P2-type promoter occasionally occurs within the human genome. Furthermore, 35 DNA fragments corresponding to putative promoters of non-protein-coding transcripts (ncRNAs) shared similar features with the P2 in both promoter activities and sequence compositions. At least, a part of ncRNAs, which have been massively identified by full-length cDNA projects with no functional relevance inferred, may have originated from those sporadic promoter activities of primary DNA sequences inherent to the human genome

Plywood-Like Structure Of Injection-Moulded Polypropylene

Injection-moulded products having unique structure, in which the direction of molecular orientation in the skin layer is perpendicular to that in the core layer, are developed employing isotactic polypropylene with a nucleating agent. The extraordinary three-layered structure with β trigonal crystal form in the core layer, which shows higher impact strength than the conventional α monoclinic form, leads to high level of toughness. Moreover, an injection-moulded product having five-layered structure is also demonstrated in this paper. Because of the complicated crack propagation nature due to the abrupt change of molecular orientation, which avoids fractured pieces with sharp-edge, the products with plywood-likestructure will be employed in various applications to improve the safety

The Usefulness of Mandibular and Maxillary Bone Derived from Neural Crest as Bone Graft Substitutes

Autografts, which are commonly used for alveolar bone regeneration, often utilize the ilium and jaw bones as alternative bone graft materials. Maxillary and mandibular bones are developmentally derived from neural crest-derived cells (NCDCs), while the majority of trunk and limb bones are derived from mesoblast cells. Consequently, the host bone graft material might differ in developmental origin from the recipient bone. With such a potential mismatch in practical terms, it is unclear whether genuine jaw bone can be regenerated. We hypothesized that bones derived from NCDCs and mesoblast cells show different capacities for in vivo bone healing. To investigate this proposal, we undertook bone graft experiments using a murine model. We first perforated a 2-mm diameter area in both the frontal and parietal bones, which are derived from NCDCs and mesoblast cells, respectively; then we grafted various source materials into each bone defect. Mice were euthanized at 2 weeks after grafting, and histological analyses and immunohistochemistry were performed to evaluate differences in bone healing based on the various combinations of graft and recipient bones. The frontal bone was found to heal faster than the parietal bone. Parietal bone defects transplanted with maxillary and mandibular bone grafts exhibited closure, whereas iliac and femoral bone grafts did not result in full healing. Immunostaining for osteopontin also demonstrated good bone regeneration in the parietal bone defects using maxillary and mandibular bone graft materials. These results suggest that maxilla and mandible bones exhibit NCDC properties with an enhanced healing potential. We conclude that maxillary and mandibular bones are effective bone graft and graft bed materials

Association between number of medications and hip fractures in Japanese elderly using conditional logistic LASSO regression

Abstract To examine the association between hip fracture and associated factors, including polypharmacy, and develop an optimal predictive model, we conducted a population-based matched case–control study using the health insurance claims data on hip fracture among Japanese patients. We included 34,717 hospitalized Japanese patients aged ≥ 65 years with hip fracture and 34,717 age- and sex- matched controls who were matched 1:1. This study included 69,434 participants. Overall, 16 variable comorbidities and 60 variable concomitant medications were used as explanatory variables. The participants were added to early elderly and late elderly categories for further analysis. The odds ratio of hip fracture increased with the number of medications only in the early elderly. AUC was highest for early elderly (AUC, 0.74, 95% CI 0.72–0.76). Use of anti-Parkinson’s drugs had the largest coefficient and was the most influential variable in many categories. This study confirmed the association between risk factors, including polypharmacy and hip fracture. The risk of hip fracture increased with an increase in medication number taken by the early elderly and showed good predictive accuracy, whereas there was no such association in the late elderly. Therefore, the early elderly in Japan should be an active target population for hip fracture prevention

Influence of Npc1 genotype on the toxicity of hydroxypropyl-β-cyclodextrin, a potentially therapeutic agent, in Niemann–Pick Type C disease models

Hydroxypropyl-β-cyclodextrin (HPBCD) is an attractive drug candidate against Niemann–Pick Type C (NPC) disease. However, the safety of HPBCD treatment for NPC patients remains to be elucidated. In this study, we examined the acute toxicity of HPBCD in Npc1-deficient mice. When treated with HPBCD (20,000 mg/kg, subcutaneously), over half of the wild-type (Npc1+/+) or Npc1+/− mice died by 72 h after the injection. In contrast, all of the Npc1−/− mice survived. Marked pathophysiological changes, such as an elevation in serum transaminase and creatinine levels, hepatocellular necrosis, renal tubular damage, interstitial thickening, and hemorrhages in lungs, were induced by the HPBCD treatment in Npc1+/+ or Npc1+/− mice. However, these pathophysiological changes were significantly alleviated in Npc1−/− mice. In addition, in vitro analysis showed that the Npc1 gene deficiency and treatment with U18666A, an Npc1 inhibitor, remarkably attenuated the cytotoxicity of HPBCD in Chinese hamster ovary cells. These results suggest that the NPC1 genotype exacerbates the cytotoxicity of HPBCD and Npc1−/− mice have substantial resistance to the lethality and the organ injury induced by HPBCD injection compared with Npc1+/+ or Npc1+/− mice. We suggest that the Npc1 genotype should be considered in the safety evaluation of HPBCD using experimental animals and cells