Glucose induces FGF21 mRNA expression through ChREBP activation in rat hepatocytes

Fibroblast growth factor 21 (FGF21) has beneficial effects of improving the plasma glucose and lipid profiles in diabetic rodents. Here, we investigated carbohydrate response element binding protein (ChREBP) involvement in the regulation of FGF21 mRNA expression in liver. Glucose stimulation and adenoviral overexpression of dominant active ChREBP increased FGF21 mRNA. Consistently, adenoviral expression of dominant negative Mlx inhibited glucose induction of FGF21 mRNA. Furthermore, deletion studies of mouse FGF21 gene promoter (−2000 to +65 bp) revealed a glucose responsive region between −74 and −52 bp. These findings suggest that FGF21 expression is regulated by ChREBP.     

Gait analysis using gravitational acceleration measured by wearable sensors

A novel method for measuring human gait posture using wearable sensor units is proposed. The sensor units consist of a tri-axial acceleration sensor and three gyro sensors aligned on three axes. The acceleration and angular velocity during walking were measured with seven sensor units worn on the abdomen and the lower limb segments (both thighs, shanks and feet). The three-dimensional positions of each joint are calculated from each segment length and joint angle. Joint angle can be estimated mechanically from the gravitational acceleration along the anterior axis of the segment. However, the acceleration data during walking includes three major components; translational acceleration, gravitational acceleration and external noise. Therefore, an optimization analysis was represented to separate only the gravitational acceleration from the acceleration data. Because the cyclic patterns of acceleration data can be found during constant walking, a FFT analysis was applied to obtain some characteristic frequencies in it. A pattern of gravitational acceleration was assumed using some parts of these characteristic frequencies. Every joint position was calculated from the pattern under the condition of physiological motion range of each joint. An optimized pattern of the gravitational acceleration was selected as a solution of an inverse problem. Gaits of three healthy volunteers were measured by walking for 20 s on a flat floor. As a result, the acceleration data of every segment was measured simultaneously. The characteristic three-dimensional walking could be shown by the expression using a stick figure model. In addition, the trajectories of the knee joint in the horizontal plane could be checked by visual imaging on a PC. Therefore, this method provides important quantitive information for gait diagnosis.     

The impact of measurement errors in the identification of regulatory networks

Background  

There are several studies in the literature depicting measurement error in gene expression data and also, several others about regulatory network models. However, only a little fraction describes a combination of measurement error in mathematical regulatory networks and shows how to identify these networks under different rates of noise.     

Characterization of teleost Mdga1 using a gene‐trap approach in medaka (Oryzias latipes)

MAM domain containing glycosilphosphatidilinositol anchor 1 (MDGA1) is an IgCAM protein present in many vertebrate species including humans. In mammals, MDGA1 is expressed by a subset of neurons in the developing brain and thought to function in neural cell migration. We identified a fish ortholog of mdga1 by a gene‐trap screen utilizing the Frog Prince transposon in medaka (Japanese killifish, Oryzias latipes). The gene‐trap vector was inserted into an intronic region of mdga1 to form a chimeric protein with green fluorescent protein, allowing us to monitor mdga1 expression in vivo. Expression of medaka mdga1 was seen in various types of embryonic brain neurons, and specifically in neurons migrating toward their target sites, supporting the proposed function of MDGA1. We also isolated the closely related mdga2 gene, whose expression partially overlapped with that of mdga1. Despite the fact that the gene‐trap event eliminated most of the functional domains of the Mdga1 protein, homozygous embryos developed normally without any morphological abnormality, suggesting a functional redundancy of Mdga1 with other related proteins. High sequential homology of MDGA proteins between medaka and other vertebrate species suggests an essential role of the MDGA gene family in brain development among the vertebrate phylum. genesis 47:505–513, 2009. © 2009 Wiley‐Liss, Inc.     

Recursive regularization for inferring gene networks from time-course gene expression profiles

Background  

Inferring gene networks from time-course microarray experiments with vector autoregressive (VAR) model is the process of identifying functional associations between genes through multivariate time series. This problem can be cast as a variable selection problem in Statistics. One of the promising methods for variable selection is the elastic net proposed by Zou and Hastie (2005). However, VAR modeling with the elastic net succeeds in increasing the number of true positives while it also results in increasing the number of false positives.     

Mycobacteria Exploit Host Hyaluronan for Efficient Extracellular Replication

In spite of the importance of hyaluronan in host protection against infectious organisms in the alveolar spaces, its role in mycobacterial infection is unknown. In a previous study, we found that mycobacteria interact with hyaluronan on lung epithelial cells. Here, we have analyzed the role of hyaluronan after mycobacterial infection was established and found that pathogenic mycobacteria can grow by utilizing hyaluronan as a carbon source. Both mouse and human possess 3 kinds of hyaluronan synthases (HAS), designated HAS1, HAS2, and HAS3. Utilizing individual HAS-transfected cells, we show that HAS1 and HAS3 but not HAS2 support growth of mycobacteria. We found that the major hyaluronan synthase expressed in the lung is HAS1, and that its expression was increased after infection with Mycobacterium tuberculosis. Histochemical analysis demonstrated that hyaluronan profoundly accumulated in the granulomatous legion of the lungs in M. tuberculosis-infected mice and rhesus monkeys that died from tuberculosis. We detected hyaluronidase activity in the lysate of mycobacteria and showed that it was critical for hyaluronan-dependent extracellular growth. Finally, we showed that L-Ascorbic acid 6-hexadecanoate, a hyaluronidase inhibitor, suppressed growth of mycobacteria in vivo. Taken together, our data show that pathogenic mycobacteria exploit an intrinsic host-protective molecule, hyaluronan, to grow in the respiratory tract and demonstrate the potential usefulness of hyaluronidase inhibitors against mycobacterial diseases.     

Genetic Evidence That the Non-Homologous End-Joining Repair Pathway Is Involved in LINE Retrotransposition

Long interspersed elements (LINEs) are transposable elements that proliferate within eukaryotic genomes, having a large impact on eukaryotic genome evolution. LINEs mobilize via a process called retrotransposition. Although the role of the LINE-encoded protein(s) in retrotransposition has been extensively investigated, the participation of host-encoded factors in retrotransposition remains unclear. To address this issue, we examined retrotransposition frequencies of two structurally different LINEs—zebrafish ZfL2-2 and human L1—in knockout chicken DT40 cell lines deficient in genes involved in the non-homologous end-joining (NHEJ) repair of DNA and in human HeLa cells treated with a drug that inhibits NHEJ. Deficiencies of NHEJ proteins decreased retrotransposition frequencies of both LINEs in these cells, suggesting that NHEJ is involved in LINE retrotransposition. More precise characterization of ZfL2-2 insertions in DT40 cells permitted us to consider the possibility of dual roles for NHEJ in LINE retrotransposition, namely to ensure efficient integration of LINEs and to restrict their full-length formation.     

Relationship between species richness and spatial and temporal distance from seed source in semi‐natural grassland

Question: How do traditional management practices of field margins maintain the biodiversity of native grassland species? Location: Semi‐natural grassland on the field margins of traditional and consolidated agricultural fields on Awaji Island, central Japan. Methods: The distance to the nearest traditional field margin to the study sites was determined because the traditional field was considered as a seed source of native vegetation to the semi‐natural grasslands under study. We selected field margins in consolidated fields of different ages and distances from seed sources. Indicator species for both field types were sought. Regression analysis and detrended correspondence analysis (DCA) were used to determine the effect of spatial and temporal distances on the species composition of native vegetation. Results: Species richness differed significantly between the margin of traditional and consolidated fields. We identified significant indicator species of traditional fields, but not of consolidated fields. In consolidated fields, species richness increased significantly with age and decreased significantly with increasing distance to the source. At younger sites, species richness decreased faster with distance to the source because of strong negative correlation, but not at older sites. DCA ordination plots similarly indicated that similarities of vegetation composition in consolidated and traditional fields decreased with distance, and the effect of distance decreased with age. Conclusions: The species composition of the grassland margins of consolidated field was more similar to the margins of traditional fields if the consolidated fields were older, and/or closer to traditional fields. This pattern suggests that dispersal may play a role in the establishment of species on field margins.