Hidenori Inaoka

Inter-Species Differences of Co-expression of Neighboring Genes in Eukaryotic Genomes

BackgroundThere is increasing evidence that gene order within the eukaryotic genome is not random. In yeast and worm, adjacent or neighboring genes tend to be co-expressed. Clustering of co-expressed genes has been found in humans, worm and fruit flies. However, in mice and rats, an effect of chromosomal distance (CD) on co-expression has not been investigated yet. Also, no cross-species comparison has been made so far. We analyzed the effect of CD as well as normalized distance (ND) using expression data in six eukaryotic species: yeast, fruit fly, worm, rat, mouse and human.ResultsWe analyzed 24 sets of expression data from the six species. Highly co-expressed pairs were sorted into bins of equal sized intervals of CD, and a co-expression rate (CoER) in each bin was calculated. In all datasets, a higher CoER was obtained in a short CD range than a long distance range. These results show that across all studied species, there was a consistent effect of CD on co-expression. However, the results using the ND show more diversity. Intra- and inter-species comparisons of CoER reveal that there are significant differences in the co-expression rates of neighboring genes among the species. A pair-wise BLAST analysis finds 8 – 30 % of the highly co-expressed pairs are duplic ated genes.ConclusionWe confirmed that in the six eukaryotic species, there was a consistent tendency that neighboring genes are likely to be co-expressed. Results of pair-wised BLAST indicate a significant effect of non-duplicated pairs on co-expression. A comparison of CD and ND suggests the dominant effect of CD.

Human standing posture control system depending on adopted strategies

Control of the standing posture of humans involves at least two distinct modes of operation to restore the body balance in the sagittal plane: the ankle strategy and the hip strategy. The objective of the study was to estimate the contribution of vestibular, visual and somatosensory feedbacks to these distinct strategies. The body dynamics was described as the motion of two linked rigid segments that represented the legs and the rest of the body. The posture controller received the inclination angles of the two body segments as inputs and regulated the moments around the ankle and hip joints. The controller had four feedback paths that were characterised by transfer functions connecting the two inputs and the two outputs. To evoke the distinct strategies, the floor conditions were varied by narrowing the support surface under the feet. A continuous pseudo-random external disturbing force was applied to the waist and the thigh independently. The inclination angles of the body segments and the ground reaction force were measured, and the transfer functions of the controller were estimated with the maximum-likelihood system identification procedure. Six healthy male adult subjects participated in the experiment. When the hip strategy became evident under the narrow support surface conditions, the transfer function relating the leg inclination angle and the ankle joint moment decreased its DC gain (16%), whereas the other three transfer functions increased the gains (20–140%) (ANOVA, p<0.05). Based on a criterion for simplicity in the modification of the posture controller, these changes suggest a new hypothesis that, when posture control becomes difficult, the central nervous system selectively activates the somatosensory feedback paths from the hip joint angle to the moments around the ankle and hip joints.

Lower expression of genes near microRNA in C. elegans germline

BackgroundMicroRNAs (miRNAs) are recently discovered short non-protein-coding RNA molecules. miRNAs are increasingly implicated in tissue-specific transcriptional control and particularly in development. Because there is mounting evidence for the localized component of transcriptional control, we investigated if there is a distance-dependent effect of miRNA.ResultsWe analyzed gene expression levels around the 84 of 113 know miRNAs for which there are nearby gene that were measured in the data in two independent C. elegans expression data sets. The expression levels are lower for genes in the vicinity of 59 of 84 (71%) miRNAs as compared to genes far from such miRNAs. Analysis of the genes with lower expression in proximity to the miRNAs reveals increased frequency matching of the 7 nucleotide seeds of these miRNAs.ConclusionWe found decreased messenger RNA (mRNA) abundance, localized within a 10 kb of chromosomal distance of some miRNAs, in C. elegans germline. The increased frequency of seed matching near miRNA can explain, in part, the localized effects.

Why do a wide variety of animals retain multiple isoforms of cyclooxygenase

Cyclooxygenase (COX) has been cloned from the phyla Cnidaria, Mollusca, Arthropoda, and Chordata of the animal kingdom. Many organisms have multiple COX isoforms that have arisen from gene duplication. It is not well understood why there are multiple COX isoforms in the same organism, or when duplication of the COX gene occurred. Here, we summarize the current knowledge of the evolutionary history of COX in the animal kingdom and discuss the reasons why the multiple COX system has been retained so widely. The phylogenetic analysis suggests that all COX genes in animals may descend from a common ancestor and that the duplication of an ancestral COX gene might occur within each lineage after the divergence of the animal. In most instances, the expressions of multiple COX isoforms are separately regulated and these isoforms play different and important pathophysiological roles in each organism. This may be the reason why multiple COX isoforms are widely retained.

Cross-coupling in a body-translating reaction: interaural optokinetic stimulation reflects a gravitational cue

Conclusion. The velocity storage integrator does not play a dominant role in the postural response to vertical visual cues; more likely, retinal slip provides the main driving force. By contrast, sideways eye movement can drive the velocity storage integrator and preserve a gravitational cue, which would be observed as a cross-coupling effect on the postural response. Objectives. To investigate the mechanism by which optokinetic stimulation causes the body to translate and to determine whether the optokinetic information is accompanied by a gravitational cue, which would appear as a cross-coupling effect. Materials and methods. Directionally diverse optokinetic stimuli were presented to seven healthy subjects, with and without a fixation target, and the body-translation of the subjects was recorded. Results. Horizontal optokinetic stimulation with a fixation target caused the body to translate in the same direction as the optic flow. Upward or downward vertical optokinetic stimulation caused the body to translate backward or forward, respectively, only when a fixation target was present. When the subjects interaural axis was parallel to the optokinetic flow, diagonal optokinetic stimulation in the absence of a fixation target elicited responses in the pitch plane similar to those elicited by vertical stimulation in the presence of a fixation target.

Evidence of spatially bound gene regulation in Mus musculus: Decreased gene expression proximal to microRNA genomic location

The extent, spatially and in time, of the phenomenon of localized decreased expression in the chromosomal vicinity of microRNA (miRNA) previously described in Caenorhabditis elegans is reproduced in Mus musculus across a wide range of tissues in several independent experiments. Computationally predicted miRNA targets are enriched in the vicinity of miRNAs, and transcription factors are identified as the class of genes that systematically exhibit this localized decrease. Also, those mRNA with AT-rich UTRs, particularly those that are not in the vicinity of CpG islands, most often exhibit this localized decrease. This localization broadens with the shift from developing to mature/differentiated tissues and suggests a developmentally controlled and spatially bound regulation.

Pose estimation of artificial hip joint using a single radiographic projection.

Total hip joint arthroplasty is commonly used in cases of osteoarthritis and rheumatoid arthritis. A hip joint prosthesis consists of a cup and a stem. The relative pose (position and orientation) of the prosthesis, when the patient is standing naturally, is planned pre-operatively; however, there is no guarantee that the pre-operatively planned pose will be accurate. Prosthesis component malposition, which is inadequate positioning of the acetabular or femoral component, results in limited joint movement and a large prosthetic joint contact area, and this can cause dislocation of the femoral head from the cap. Because the range of motion after total hip joint arthroplasty is determined by the relative pose of the cup and the stem, it is important to know the relative pose after hip arthroplasty. Several pose estimation methods using single-plane fluoroscopy or conventional roentgenography have been proposed. Because a conventional radiograph system is commonly used at small cost, a method using conventional radiograms is desirable for use in a clinical setting. In this study, a pose estimation method using conventional radiography is proposed, and anin vitro experiment is performed to evaluate its accuracy. The rotational errors of the relative pose of the cup with respect to the stem were smaller than 2.3°.

Temporal change in IL-6 mRNA and protein expression produced by cyclic stretching of human pulmonary artery endothelial cells

The time courses of interleukin (IL)-6 gene expression and protein production were examined in human pulmonary artery endothelial cells (HPAECs) subjected to cyclic stretching. IL-6 protein was increased even in cells without stretching. Fold changes determined by dividing the level of IL-6 protein in stretched cells by that in unstretched cells at the same sampling times indicated that IL-6 protein was increased by stretching. At least 1 h of stretching was necessary to elicit an increase of IL-6 protein, and the levels peaked at 3 h after the start of stretching. After withdrawal of stretching, there was no further increase of IL-6 protein. The expression levels of the IL-6 gene were significantly increased by stretching and peaked at 30 min after the start of stretching. The difference in the peak times of IL-6 gene and protein expression likely reflects the process of protein synthesis after the appearance of IL-6 mRNA.

Adaptive thresholds to detect differentially expressed genes in microarray data

To detect changes in gene expression data from microarrays, a fixed threshold for fold difference is used widely. However, it is not always guaranteed that a threshold value which is appropriate for highly expressed genes is suitable for lowly expressed genes. In this study, aiming at detecting truly differentially expressed genes from a wide expression range, we proposed an adaptive threshold method (AT). The adaptive thresholds, which have different values for different expression levels, are calculated based on two measurements under the same condition. The sensitivity, specificity and false discovery rate (FDR) of AT were investigated by simulations. The sensitivity and specificity under various noise conditions were greater than 89.7% and 99.32%, respectively. The FDR was smaller than 0.27. These results demonstrated the reliability of the method.

Adaptive threshold for detecting differentially expressed genes in microarray data - a simulation study to investigate its performance

To detect changes in gene expression data from DNA microarrays, a fixed threshold value is used in various studies. However, it is not always guaranteed that a threshold value which is appropriate for highly expressed genes is suitable for genes with low expression. To address this issue, we have proposed adaptive threshold, which has different values for different expression levels. In this study, the performance of the adaptive threshold method was investigated through simulations. The sensitivity in various noise conditions was in a range between 72.7 and 100% while the specificity was better than 99% for all noise conditions. These results demonstrated the good performance of the proposed method.