The retinol-retinoic acid metabolic pathway is impaired in the lumbar spine of a rat model of congenital kyphoscoliosis

Although congenital scoliosis is defined as a genetic disease characterized by a congenital and abnormal curvature of the spinal vertebrae, our knowledge of the genetic underpinnings of the disease is insufficient. We herein show that the downregulation of the retinol-retinoic acid metabolism pathway is involved in the pathogenesis of congenital scoliosis. By analyzing DNA microarray data, we found that the expression levels of genes associated with the retinol metabolism pathway were decreased in the lumbar spine of Ishibashi rats (IS), a rat model of congenital kyphoscoliosis. The expression of Adh1 and Aldh1a2 (alcohol dehydrogenase), two enzymes that convert retinol to retinoic acid in this pathway, were decreased at both the gene and protein levels. Rarα, a receptor of retinoic acid and bone morphogenetic protein 2, which play a central role in bone formation and are located downstream of this pathway, were also downregulated. Interestingly, the serum retinol levels of IS rats were higher than those of wild-type control rats. These results indicate that the adequate conversion from retinol to retinoic acid is extremely important in the regulation of normal bone formation and it may also be a key factor for understanding the pathogenesis of congenital scoliosis.     

Fluctuation of the zooplankton community in Lake Biwa during the 20th century: a paleolimnological analysis

Detailed zooplankton records from a 26-cm sediment core with a time resolution of approximately 3–10 years were obtained from Lake Biwa, Japan, to examine the historical variations in the zooplankton community during the 20th century. In the sediments, selected zooplankton remains have fluctuated over the years. Daphnia – large zooplankton herbivores – did not occur from 1900 to 1920, and formed a very minor component of the zooplankton community in the following 30 years, while Bosmina – small zooplankton herbivores – were common during this period. In the mid-1960s, however, when eutrophication was noticeable in this lake, Daphnia numbers increased dramatically and became the dominant zooplankton thereafter. In contrast, Difflugia brevicolla and D. biwae, two amoeboid protozoans that live in connection with the lake bottom environment, occurred abundantly until the late 1950s, but gradually decreased after the mid-1960s. In particular, D. biwae, a species peculiar to this lake, was not found in sediment dated after 1980, suggesting its extinction. These results indicate that the zooplankton community structure changed greatly in the 1960s, and suggest that the eutrophication occurring at this time altered the relative strength of top-down and bottom-up forces on the zooplankton community in Lake Biwa.     

Environmental control of the seasonal life cycle of a zoophytophagous mirid, <Emphasis Type="Italic">Adelphocoris triannulatus</Emphasis> (Hemiptera: Miridae)

Adelphocoris triannulatus (Stål) (Heteroptera: Miridae) is a zoophytophagous bug that inhabits grasslands and crop fields, and is widely distributed in eastern Asia. In this study, the seasonal occurrence and environmental factors controlling the seasonal life cycle of this bug were investigated in a local population in southern Kyushu, Japan. When insects were reared under different photoperiods at 20 and 25 °C, they produced diapause or nondiapause eggs depending on the photoperiod: when reared under short-day photoperiods (≤?13 h/day), females laid diapause eggs, whereas they laid nondiapause eggs when reared under long-day photoperiods (≥?14 h/day). Because the developmental duration of the pre-adult stages and maturation (minimum duration of one generation) is estimated to be approximately 30 days at summer temperatures, these results suggest that this bug has a multivoltine seasonal life cycle. In agreement with the laboratory results, only nondiapause eggs were produced until mid-August in the field, and an increasing proportion of diapause eggs were produced from early September. In addition to these findings, field sampling from spring to autumn in 2009 indicated that three or four generations were produced in one year. These results suggest that egg diapause plays a role in preventing nymphs of A. triannulatus from developing in winter, and thereby ensures the survival of the population in adverse seasons.     

Impact of insulin resistance on enhanced monocyte adhesion to endothelial cells and atherosclerogenesis independent of LDL cholesterol level

Epidemiological studies suggest that insulin resistance is an independent risk factor for cardiovascular disease. However, there is little information on the role of insulin resistance in atherosclerogenesis independent of LDL cholesterol level. The aim of this study was to investigate the impact of systemic insulin resistance on monocyte adhesion to endothelial cells and atherosclerotic lesions independent of LDL cholesterol level. KKAy mice are obese mice with spontaneous diabetes and insulin resistance, and normal levels of LDL cholesterol. In parallel with systemic insulin resistance, decreased insulin signal, and the increased expression of monocyte chemoattractant protein-1 (MCP-1) were noted in macrophages isolated from KKAy mice. These mice showed enhanced monocyte adhesion to the endothelial cells of the thoracic artery. Furthermore, these mice showed expanded atherosclerotic lesions when fed high cholesterol diet. Our data indicate that insulin resistance promotes the atherosclerogenesis independent of LDL cholesterol level. Decreased insulin signaling in macrophages associated with systemic insulin resistance could be involved, at least in part, in this pathological process.     

Formation of collagen fibrils in vitro by cleavage of procollagen with procollagen proteinases

A new system was developed for studying the assembly of collagen fibrils in vitro. A partially purified enzyme preparation containing both procollagen N-proteinase and c-proteinase (EC 3.4.24.00) activities was used to initiate fibril formation by removal of the N- and C-propeptides from type I procollagen in a physiological buffer at 35-37 degrees C. The kinetics of fibril formation were similar to those observed for fibril formation with tissue-extracted collagen in the same buffer system, except that the lag phase was longer. The longer lag phase was in part accounted for by the time required to convert procollagen to collagen. Similar results were obtained when an intermediate containing the C-propeptide but not the N-propeptide was used as a substrate. Therefore, removal of the c-propeptide appeared to be the critical step for fibril formation under the conditions used here. The fibrils formed by enzymic cleavage of procollagen or pCcollagen appeared microscopically to be more tightly packed than fibrils formed directly from collagen under the same conditions. This impression was confirmed by the observation that the fibrils formed by cleavage of procollagen were stable to temperatures 1.5-2 degrees C higher than fibers formed from extracted collagen under the same conditions. When smaller amounts of procollagen proteinase were used, the rate of cleavage of procollagen to collagen was markedly reduced. The fibrils which formed under these conditions were up to 3 micrometers in diameter. Some appeared to contain branch points.     

Significant interaction between LRP2 rs2544390 in intron 1 and alcohol drinking for serum uric acid levels among a Japanese population

A genome-wide association study identified that LRP2 rs2544390 in intron 1 was associated with serum uric acid (SUA) levels among Japanese, as well as polymorphisms of SLC22A12, ABCG2, and SLC2A9. This study aimed to confirm the association of rs2544390 C/T with SUA, as well as another LRP2 polymorphism (rs3755166 G/A) in the promoter. Subjects were 5016 health checkup examinees (3409 males and 1607 females) aged 35 to 69years with creatinine<2.0mg/dL. The subjects with SLC22A12 258WW, SLC2A9 rs11722228C allele, ABCG2 126QQ and 141Q allele (2546 males and 1199 females) were selected for analysis. Mean SUA was 6.03mg/dL for CC, 6.18mg/dL for CT, and 6.19mg/dL for TT among males (p=0.012), and 4.49mg/dL, 4.45mg/dL, and 4.42mg/dL among females (not significant), respectively. No association was observed for rs3755166. The association with rs2544390 was stronger among male drinkers. The odds ratio of drinking ≥5/week relative to no drinking for hyperuricemia (SUA≥7mg/dL and/or under medication for hyperuricemia) was 1.11 (95% confidence interval, 0.67-1.84) among CC males, 1.75 (1.22-2.51) among CT males, and 3.13 (1.80-5.43) among TT males. The interaction terms with drinking ≥5/week were 1.56 (p=0.156) for CT and 2.87 (p=0.005) for TT. This was the first report on the interaction between LRP2 genotype and alcohol drinking for SUA. Since the low density lipoprotein-related protein 2 (megalin) encoded by LRP2 is a multi-ligand endocytic receptor expressed in many tissues including the kidney proximal tubules, the association/interaction remained to be confirmed both epidemiologically and biologically.     

Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction

Mesenchymal stem cells are multipotent cells that can differentiate into cardiomyocytes and vascular endothelial cells. Here we show, using cell sheet technology, that monolayered mesenchymal stem cells have multipotent and self-propagating properties after transplantation into infarcted rat hearts. We cultured adipose tissue-derived mesenchymal stem cells characterized by flow cytometry using temperature-responsive culture dishes. Four weeks after coronary ligation, we transplanted the monolayered mesenchymal stem cells onto the scarred myocardium. After transplantation, the engrafted sheet gradually grew to form a thick stratum that included newly formed vessels, undifferentiated cells and few cardiomyocytes. The mesenchymal stem cell sheet also acted through paracrine pathways to trigger angiogenesis. Unlike a fibroblast cell sheet, the monolayered mesenchymal stem cells reversed wall thinning in the scar area and improved cardiac function in rats with myocardial infarction. Thus, transplantation of monolayered mesenchymal stem cells may be a new therapeutic strategy for cardiac tissue regeneration.     

Airway hyperresponsiveness through synergy of gammadelta} T cells and NKT cells

Mice sensitized and challenged with OVA were used to investigate the role of innate T cells in the development of allergic airway hyperresponsiveness (AHR). AHR, but not eosinophilic airway inflammation, was induced in T cell-deficient mice by small numbers of cotransferred gammadelta T cells and invariant NKT cells, whereas either cell type alone was not effective. Only Vgamma1+Vdelta5+ gammadelta T cells enhanced AHR. Surprisingly, OVA-specific alphabeta T cells were not required, revealing a pathway of AHR development mediated entirely by innate T cells. The data suggest that lymphocytic synergism, which is key to the Ag-specific adaptive immune response, is also intrinsic to T cell-dependent innate responses.