Quantitative modeling of regular retinal microglia distribution.

Microglia are resident immune cells in the central nervous system, showing a regular distribution. Advancing microscopy and image processing techniques have contributed to elucidating microglia's morphology, dynamics, and distribution. However, the mechanism underlying the regular distribution of microglia remains to be elucidated. First, we quantitatively confirmed the regularity of the distribution pattern of microglial soma in the retina. Second, we formulated a mathematical model that includes factors that may influence regular distribution. Next, we experimentally quantified the model parameters (cell movement, process formation, and ATP dynamics). The resulting model simulation from the measured parameters showed that direct cell-cell contact is most important in generating regular cell spacing. Finally, we tried to specify the molecular pathway responsible for the repulsion between neighboring microglia.

Mathematical modeling of palatal suture pattern formation: morphological differences between sagittal and palatal sutures.

The median palatal suture serves as a growth center for the maxilla; inadequate growth at this site causes malocclusion and dental crowding. However, the pattern formation mechanism of palatal sutures is poorly understood compared with that of calvarial sutures such as the sagittal suture. In the present study, therefore, we compared the morphological characteristics of sagittal and palatal sutures in human bone specimens. We found that palatal suture width was narrower than sagittal suture width, and the interdigitation amplitude of the palatal suture was lower than that of the sagittal suture. These tendencies were also observed in the neonatal stage. However, such differences were not observed in other animals such as chimpanzees and mice. We also used a mathematical model to reproduce the differences between palatal and sagittal sutures. After an extensive parameter search, we found two conditions that could generate the difference in interdigitation amplitude and suture width: bone differentiation threshold [Formula: see text] and growth speed c. We discuss possible biological interpretations of the observed pattern difference and its cause.

Noise-induced scaling in skull suture interdigitation.

Sutures, the thin, soft tissue between skull bones, serve as the major craniofacial growth centers during postnatal development. In a newborn skull, the sutures are straight; however, as the skull develops, the sutures wind dynamically to form an interdigitation pattern. Moreover, the final winding pattern had been shown to have fractal characteristics. Although various molecules involved in suture development have been identified, the mechanism underlying the pattern formation remains unknown. In a previous study, we reproduced the formation of the interdigitation pattern in a mathematical model combining an interface equation and a convolution kernel. However, the generated pattern had a specific characteristic length, and the model was unable to produce a fractal structure with the model. In the present study, we focused on the anterior part of the sagittal suture and formulated a new mathematical model with time-space-dependent noise that was able to generate the fractal structure. We reduced our previous model to represent the linear dynamics of the centerline of the suture tissue and included a time-space-dependent noise term. We showed theoretically that the final pattern from the model follows a scaling law due to the scaling of the dispersion relation in the full model, which we confirmed numerically. Furthermore, we observed experimentally that stochastic fluctuation of the osteogenic signal exists in the developing skull, and found that actual suture patterns followed a scaling law similar to that of the theoretical prediction.

Case report reconstruction of exposed ilium with reverse turnover latissimus dorsi muscle flap.

OBJECTIVE: It is difficult to cover a large skin and soft tissue defect with exposure of the ilium. We therefore performed a new reconstruction technique, using a reverse latissimus dorsi muscle flap fed by perforating branches of only the 10th intercostal artery. METHODS: A 45-year-old man had a large traumatic defect located on the hip with exposure of the iliac crest. After confirming and preserving perforating branches of the 10th intercostal artery, the latissimus dorsi muscle flap was turned over just proximal to the perforating branch, and a split-thickness skin graft was performed over the flap. RESULTS: The skin graft took place well and there were no circulation problems. CONCLUSIONS: This flap covered a larger area on the hip than the musculocutaneous flap. Furthermore, this is easier to perform and is less invasive than a vascularized free flap. Skin and soft tissue defects that expose bones of the lumbar or hip region can be reconstructed with a local flap; however, the deficit is small for this coverage and usually there is little skin and soft tissue to cover the wound defect in the surrounding area. Thus, it is often difficult to deal with large defects. We performed a reconstruction, using a reverse latissimus dorsi flap fed by perforating branches of the 10th intercostal artery for a large skin and soft tissue defect of the hip with exposure of the iliac crest, resulting in a good outcome. This technique is thought to be useful for reconstruction when the ilium is exposed, and we report the case and surgical procedure.

Regulation of clathrin-mediated endocytosis by p53.

The p53 gene encodes a multi-functional protein to prevent tumorigenesis. Although there have been many reports of the nuclear functions of p53, little is known about the cytosolic functions of p53. Here, we found that p53 is present in cytosol as well as nuclei under unstressed conditions and binds to clathrin heavy chain (CHC). CHC is known to play a role in receptor-mediated endocytosis. Based on our findings, we examined the effect of p53 on clathrin-mediated endocytosis of epidermal growth factor receptor (EGFR). Surprisingly, p53 co-localized with CHC at the plasma membrane in response to EGF stimulation. In cells with ablated p53 expression by RNAi, EGFR internalization was delayed and intracellular signaling from EGFR was altered. Thus, our findings provide evidence that cytosolic p53 may participate in the regulation of clathrin-mediated endocytosis to control the correct signaling from EGFR.

Safety evaluation of hypoallergenic wheat flour by using a DNA microarray.

The effect of the consumption of hypoallergenic wheat flour (HWF) on the expression of a wide spectrum of genes was analyzed by using a DNA microarray. Gene expression profiles in the liver and intestines of rats fed on a diet composed mainly of HWF were compared with those of rats fed on a normal flour-based diet. Among the eight thousand transcripts represented on the GeneChip microarray, no more than 30 genes exhibited up- or down-regulation of two-fold or more after one week or two months of HWF consumption. No adverse effects were apparent. Up-regulation of some of the genes known to respond to the interferon-gamma signal was apparent in the one-week experiment, which may be related to possible oral immunotolerance resulting from HWF feeding. This DNA microarray technology presents an efficient method for evaluating the safety of foods.

DNA microarray analyses of the effects of dietary proteins.

Dietary proteins and amino acids serve not only as a building block for body components but also as regulators of a variety of body functions. A great many of the functions of ingested proteins, their peptide fragments, and amino acids have been characterized and some have been brought to practical application. Using a GeneChip DNA microarray system, we first compared the gene expression profiles among rats fed on 12% casein, 12% gluten, and protein-free diets for one week. The results revealed that a few hundred genes in the liver and muscle were up- or down-regulated by more than two-fold after feeding of the gluten or the protein-free diet. Interesting findings included the induction of genes for synthesis and catabolism of cholesterol by gluten feeding. In addition, we performed a study to examine the effect of the consumption of an enzymatically produced, hypoallergenic wheat flour on gene expression profiles in rats. The results confirmed the safety of this novel food product.

Dietary protein quantity and quality affect rat hepatic gene expression.

To gain a comprehensive understanding of the molecular mechanisms underlying the effects of dietary protein on alternations in physiologic and pathologic status, the GeneChip microarray system was used to investigate the consequences of two different states of protein malnutrition on gene expression in rat liver. Expressions of 281 genes were increased or decreased by twofold or more by treatment with a protein-free diet for 1 wk compared with control rats fed a casein diet. Similarly, 111 genes were affected in rats fed a wheat gluten diet compared with those fed the casein diet. Although some of the genes identified were known to respond to protein nutrition, a majority were newly identified as responders to protein nutritional status. Interesting findings included the drastic changes in the levels of genes for Id (inhibitor of DNA binding) proteins, which are involved in the regulation of multiple genes, and of a set of genes in the pathway of cholesterol biosynthesis and disposal. This study represents a step toward a more global understanding of gene expression changes in states of protein malnutrition.