Study on Structural Changes in Tibial Cancellous Bone with Mechanical Loading After Short-term Immobilization in Rats

Summary　This study aimed to investigate effects of exercise and immobilization just before the exercise on bone remodeling processes.　In experiment 1, rats were used as materials, and were divided into three groups: an exercise after immobilization group that performed 4-week-exercise after 4-day-immobilization （IM-EX）， an exercise group that accomplished 4-week-exercise （EX）， and a control that was fed normally for four weeks （CO）. In experiment 2, rats were also divided into three groups: an exercise after immobilization group that performed 1-week-exercise after 2-day-immobilization （IM-EX）， an exercise group that accomplished 1-week-exercise （EX）， and a control that was fed normally for one week（ CO）. Rats in each group were euthanized at the end of experimental period, tibiae were excised from them and those specimens were observed histologically and morphometrically.　Density and thickness of the bone trabeculae increased at primary cancellous bone from immediately after starting of experiments in IM-EX of the experiment 1 and 2. As for secondary cancellous bone, IM-EX of experiment 1 showed remarkable decrease of bone mass once after four days immobilization, and it was necessary for four weeks to reached to the same level as EX by exercise. On the other hand, in IM-EX of experiment 2, the bone mass hardly changed by two-day-immobilization but decreased temporarily after 2 and 4 days of exercise period, and then, it already recovered up to level than EX after 7 days. Many osteoblasts showed positive reaction to immunostaining of RANKL, and many TRAP positive cells were also recognized, in IM-EX of experiment 2. And, bone matrixes indicated positive reactions to immunostaining of TGF-β， in each groups.　Through the results mentioned above, it was suggested that active bone formation could be brought by the exercise following the short-term immobilization, because factors like TGF-β that promoted differentiation and activation of the osteoblasts were released from the bone matrix by acute bone resorption.Abstract　This study aimed to investigate effects of exercise and immobilization just before exercise on bone remodeling processes. Rats were used as materials, structures of their tibiae were observed through experiment 1 and 2, and following data were obtained.　It was nessesory for four weeks that bone mass of the 4-week-exercise after 4-day-immobillization group recovered to the level that of the 4-week-exercise group. The bone mass of the 1-week-exercise after 2- dayimmobilization group decreased at once, but reached higher level than 1-week-exercise group after one week of the experiment. Many RANKL and TRAP positive cells were observed after 2 days of the experiment in the1-week-exercise after 2-day-immobillization group, compared to the control, and the bone matrixes indicated positive reactions to TGF-βimmunostaining.　Then, it was suggested that the bone resorption activated, differentiation and activation factors like TGF-β were released from the bone matrixes into bone marrow, and then, this could brought active bone formation, by the exercise following the immobilization

Molecular analysis of cyclic α-maltosyl-(1→6)-maltose binding protein in the bacterial metabolic pathway

Cyclic α-maltosyl-(1→6)-maltose (CMM) is a cyclic glucotetrasaccharide with alternating α-1,4 and α-1,6 linkages. Here, we report functional and structural analyses on CMM-binding protein (CMMBP), which is a substrate-binding protein (SBP) of an ABC importer system of the bacteria Arthrobacter globiformis. Isothermal titration calorimetry analysis revealed that CMMBP specifically bound to CMM with a Kd value of 9.6 nM. The crystal structure of CMMBP was determined at a resolution of 1.47 Å, and a panose molecule was bound in a cleft between two domains. To delineate its structural features, the crystal structure of CMMBP was compared with other SBPs specific for carbohydrates, such as cyclic α-nigerosyl-(1→6)-nigerose and cyclodextrins. These results indicate that A. globiformis has a unique metabolic pathway specialized for CMM

DNA sequencing by MALDI-TOF MS using alkali cleavage of RNA/DNA chimeras

Approaches developed for sequencing DNA with detection by mass spectrometry use strategies that deviate from the Sanger-type methods. Procedures demonstrated so far used the sequence specificity of RNA endonucleases, as unfortunately equivalent enzymes for DNA do not exist and therefore require transcription of DNA into RNA prior to fragmentation

肥満によって遊離する脂肪細胞由来のDNA断片が脂肪組織の炎症とインスリン抵抗性を引き起こす

Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9−/−) macrophages. Fat-fed Tlr9−/− mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9−/− mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography–determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance

A Genome-Wide Association Study Identified AFF1 as a Susceptibility Locus for Systemic Lupus Eyrthematosus in Japanese

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs) have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8%) compared to the genome-wide SNPs (6.9%). In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1) gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10−9, odds ratio = 1.21). The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05). As AFF1 transcripts were prominently expressed in CD4+ and CD19+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset

シカク ショウガイシャ ヘ ノ シンキュウ キョウイク ニ オケル オントロジー ベース キョウザイ ノ ユウコウセイ

我々は視覚障害者向けの鍼灸、特に経絡と経穴に関する教育材料の研究に取り組んだ。この教材では、鍼灸分野における概念間の関係の体系的な理解を可能にすべく、オントロジーを用いた。オントロジーの概念図によりオントロジー教材を作成し、これを鍼灸の講義で使用した群とオントロジー教材未使用群とで経絡・経穴の試験の結果を比較し、その有効性を解析した。その結果、オントロジー教材を使用した学生の経絡・経穴の試験の得点は、オントロジー教材未使用群の学生の得点よりも有意(P < 0.001)に高く、経絡と経穴の学習にオントロジー教材有効である事が明らかになった。この結果は、オントロジーの視覚障害者教育への利用が視覚障害者の鍼灸理論の学習へも有効であることを示唆している。In this study we developed learning material of acupuncture - acupoints and meridians - for visually impaired people. For this learning material, we used ontology to construct the relations between the concepts in the acupuncture and moxibustion field which also enables tactical understanding similarly as visual understanding. We then used our learning material in the acupuncture lecture for the visually impaired students, and quantitatively analysed its efficacy to compare the results with the group which did not use the learning material. As a result, the students, who used our learning material, scored significantly higher in the examination than the students of non-use group (P < 0.001), suggesting that our learning material was effective for learning of acupuncture theory