Influence of Estrogen Receptor α

Estrogen receptor α (ERα) is one of candidate genes for osteoporosis. This study examined the influence of ERα gene, PvuII, and XbaI genotypes on bone density of calcaneus in response to habitual exercise. ERα polymorphisms were detected using PvuII and XbaI restriction enzymes in 316 Japanese postmenopausal women. The bone density was significantly lower in the women carrying PP, pp, or xx genotype without habitual exercise than in the age-matched women without those genotypes. The women carrying Pp genotype without habitual exercise had normal bone density compared to those without Pp genotype. The women carrying PPxx or ppxx polymorphism without habitual exercise had low bone density compared to those with habitual exercise. Thus, the reduction of bone density was attenuated in the women carrying PPxx or ppxx with habitual exercise. In addition, habitual exercise was highly effective for the bone density in the women carrying xx homozygote. These findings indicate that analyses of XbaI and PvuII polymorphisms of ERα may be useful to predict the effect of exercise on bone density, and habitual exercise attenuates the reduction of bone density in women with some genotypes

Regressed three-dimensional capillary network and inhibited angiogenic factors in the soleus muscle of non-obese rats with type 2 diabetes

Based on findings obtained using two-dimensional capillary analyses on tissue cross-sections, diabetes has been shown to be associated with a high risk for microangiopathy and capillary regression in skeletal muscles. We visualized the three-dimensional architecture of the capillary networks in the soleus muscle of non-obese Goto-Kakizaki (GK) rats with type 2 diabetes and compared them with those of control Wistar rats to provide novel information, e.g., capillary volume, on the capillary networks. In addition, we examined pro- and anti-angiogenic gene expression levels in the soleus muscle of GK rats using TaqMan probe-based real-time PCR. As expected, plasma glucose levels were higher and insulin levels lower in GK than control rats. The three-dimensional architecture of the capillary networks was regressed and capillary volume was smaller in the soleus muscle of GK compared to control rats. The mRNA expression levels of the pro-angiogenic factors HIF-1α, KDR, Flt-1, ANG-1, and Tie-2 were lower, whereas the level of the anti-angiogenic factor TSP-1 was higher in GK than control rats. These data suggest that a decrease in pro-angiogenic and increase in anti-angiogenic factors may play an important role in type 2 diabetes-induced muscle circulatory complications

Development of an Apparatus for Measuring the Load Acting on Joint Sealant when Movement Occurs

The sealant that fills the joints of an exterior walls of building is subjected to weather loads, such as sunlight, ambient temperature, and rain, as well as a movement of the joints. As a result, the sealant gradually deteriorates under the combined deterioration factors of weathering and movement. Meanwhile, the results of a 15-year outdoor dynamic exposure test conducted in Japan using the methodology of ISO 11617 showed that the progress of damage varies greatly depending on the type of sealant and the stress relaxation rate. However, the mechanism of damage progression is unclear. In the present study, we focused on the load when the sealant moves and developed a load-measuring apparatus as the first step in clarifying the relationship between the progress of damage and the load. The load was measured at −20, 23, and 40 °C for test specimens with different stress relaxation rates, and it was confirmed that the developed load-measuring apparatus was able to measure the load correctly. Furthermore, it was shown that it is difficult for the stress of the sealant with a high stress relaxation rate to relax over time at low temperature but easy at high temperature, and the load increases when switching from the compressed state to the extended state

Hyperbaric Oxygen Exposure Reduces Age-Related Decrease in Oxidative Capacity of the Tibialis Anterior Muscle in Mice

The effects of exposure to hyperbaric oxygen on the oxidative capacity of the skeletal muscles in mice at different ages were investigated. We exposed 5-, 34-, 55-, and 88-week-old mice to 36% oxygen at 950 mmHg for 6 hours per day for 2 weeks. The activities of succinate dehydrogenase (SDH), which is a mitochondrial marker enzyme, of the tibialis anterior muscle in hyperbaric mice were compared with those in age-matched mice under normobaric conditions (21% oxygen at 760 mmHg). Furthermore, the SDH activities of type IIA and type IIB fibers in the muscle were determined using quantitative histochemical analysis. The SDH activity of the muscle in normobaric mice decreased with age. Similar results were observed in both type IIA and type IIB fibers in the muscle. The decrease in the SDH activity of the muscle was reduced in hyperbaric mice at 57 and 90 weeks. The decreased SDH activities of type IIA and type IIB fibers were reduced in hyperbaric mice at 90 weeks and at 57 and 90 weeks, respectively. We conclude that exposure to hyperbaric oxygen used in this study reduces the age-related decrease in the oxidative capacity of skeletal muscles

Phosphatidic acid-dependent localization and basal de-phosphorylation of RA-GEFs regulate lymphocyte trafficking

Background: Lymphocytes circulate between peripheral lymphoid tissues via blood and lymphatic systems, and chemokine-induced migration is important in trafficking lymphocytes to distant sites. The small GTPase Rap1 is important in mediating lymphocyte motility, and Rap1-GEFs are involved in chemokine-mediated Rap1 activation. Here, we describe the roles and mechanisms of Rap1-GEFs in lymphocyte trafficking. Results: In this study, we show that RA-GEF-1 and 2 (also known as Rapgef2 and 6) are key guanine nucleotide exchange factors (GEF) for Rap1 in lymphocyte trafficking. Mice harboring T cell-specific knockouts of Rapgef2/6 demonstrate defective homing and egress of T cells. Sphingosine-1-phosphate (S1P) as well as chemokines activates Rap1 in a RA-GEF-1/2-dependent manner, and their deficiency in T cells impairs Mst1 phosphorylation, cell polarization, and chemotaxis toward S1P gradient. On the other hand, B cell-specific knockouts of Rapgef2/6 impair chemokine-dependent retention of B cells in the bone marrow and passively facilitate egress. Phospholipase D2-dependent production of phosphatidic acid by these chemotactic factors determines spatial distribution of Rap1-GTP subsequent to membrane localization of RA-GEFs and induces the development of front membrane. On the other hand, basal de-phosphorylation of RA-GEFs is necessary for chemotactic factor-dependent increase in GEF activity for Rap1. Conclusions: We demonstrate here that subcellular distribution and activation of RA-GEFs are key factors for a directional movement of lymphocytes and that phosphatidic acid is critical for membrane translocation of RA-GEFs with chemokine stimulation

PGC-1α mRNA Level and Oxidative Capacity of the Plantaris Muscle in Rats with Metabolic Syndrome, Hypertension, and Type 2 Diabetes

We examined the fiber profiles and the mRNA levels of peroxisome proliferator-activated receptors (PPARα and PPARδ/β) and of the PPARγ coactivator-1α (PGC-1α) in the plantaris muscles of 15-week-old control (WR), metabolic syndrome (CP), hypertensive (SHR), and type 2 diabetic (GK) rats. The deep regions in the muscles of SHR and GK rats exhibited lower percentages of high-oxidative type I and IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR and CP rats. The surface regions in the muscles of CP, SHR, and GK rats exhibited lower percentages of high-oxidative type IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR rats. The muscles of SHR and GK rats had lower oxidative enzyme activity compared with WR rats. The muscles of SHR rats had the lowest PPARδ/β mRNA level. In addition, the muscles of SHR and GK rats had lower PGC-1α mRNA level compared with WR and CP rats. We concluded that the plantaris muscles of rats with hypertension and type 2 diabetes have lower oxidative capacity, which is associated with the decreased level of PGC-1α mRNA

Robustness under Functional Constraint: The Genetic Network for Temporal Expression in Drosophila Neurogenesis

Precise temporal coordination of gene expression is crucial for many developmental processes. One central question in developmental biology is how such coordinated expression patterns are robustly controlled. During embryonic development of the Drosophila central nervous system, neural stem cells called neuroblasts express a group of genes in a definite order, which leads to the diversity of cell types. We produced all possible regulatory networks of these genes and examined their expression dynamics numerically. From the analysis, we identified requisite regulations and predicted an unknown factor to reproduce known expression profiles caused by loss-of-function or overexpression of the genes in vivo, as well as in the wild type. Following this, we evaluated the stability of the actual Drosophila network for sequential expression. This network shows the highest robustness against parameter variations and gene expression fluctuations among the possible networks that reproduce the expression profiles. We propose a regulatory module composed of three types of regulations that is responsible for precise sequential expression. This study suggests that the Drosophila network for sequential expression has evolved to generate the robust temporal expression for neuronal specification

50Mメッシュ キコウ チ ジョウホウ ト キャベツ トウガイ ノ ヒガイ ジッタイ ノ カンケイ

三浦半島のキャベツ栽培地帯では凍害の多発地区とそうでない地区が混在していることが過去16年間に渡って行われた現地調査から明らかとなっている。凍害は,基本的に最低気温が低下しやすい場所ほど発生率が高くなることから,最低気温の温度分布の実態を,50mメッシュ気温分布図によって細かく示すことができれば,省力的に半島全体の凍害発生の危険地区を把握できるとともに,適地適作を行うための基礎資料の構築が可能と考えられる。そこで,三浦半島のキャベツ栽培地帯36カ所に5分毎に計測できる温度記録計を設置し,計測日,計測時間帯を異にして収集した実測値を基にいくつかの50mメッシュ気温分布図を作成した。過去16年間に渡り毎年行ってきたキャベツの凍害実態調査結果をもとに,50mメッシュ気温分布図が凍害発生の危険地区を示すことができるかどうかを検証した。その結果,晴天,低温および弱風条件下という,とくに冷え込みが厳しい条件下でのデータを元に作成した50mメッシュ気温分布図は,凍害実態調査結果で示された凍害発生率の高い地区が他の地区よりも一段と低温になることを示すことができることが明らかとなった。一方,日中では,凍害発生率の高い地区は高温で示された。50mメッシュ気温分布図で凍害の多発地区を把握するには,このような条件を絞り込んだ上で作成する必要があると考えられた。We investigated the relationship between 50m mesh climatic information and the cabbage cold injury occurrence on cabbages cultivated in the Miura peninsula. The cold injury data of cabbage was obtained in the field investigation from 1983 to 1999. The 50m mesh climatic data was calculated based on the data collected using thermorecorders in 1998. Information of 50m mesh climatic data which show the danger area for cold injury, was that it is effective at the time of limited meteorological conditions on clear nights under low temperature and the weak wind speed. The temperature of the area where cold injury occurred at a high rate was the lowest temperature on a clear night when the wind was weak on the 50m mesh climatic data. In order to create the 50m mesh climatic charts for cold injury prevention, we must create then using the data by the temperature measurement under low temperature and weak wind speed condition on clear nights. We thought that the 50m mesh climatic information was an effective application to show the field in which cold injury is difficult to occur, and could be utilized for finding the field whose occurrence of cold injury on cabbage is low