Spatial perspective-taking is an ability to understand in which direction an object is located relative to an agent (e.g.,another person or a chair). Previous studies showed that left/right judgments prompted an egocentric transformation strategy(i.e., mental rotation of the self) whereas front/behind judgments prompted other strategies (e.g., tracing a line of sight). Toexamine whether the symmetrical shape of an agent could affect the choice of strategies, we used as an agent a cuboid whichhas a prong on one of its sides. We labeled the prong side as the front (Experiment 1) or right (Experiment 2) of the agent,about which participants made left/right and front/behind judgments. The results revealed that egocentric transformations weremore favored for judgments about directions along symmetrical than asymmetrical axes of the agent, regardless of whether thejudgment was about left/right or front/behind. This suggests similar processing underlies left/right and front/behind judgments.

Using Whitney’s Monte Carlo radiative transfer code, we simulate the near IR scattered light images in both intensity and polarized intensity for a series of axisymmetric protoplanetary disk models. By measuring the properties of the images, we study the detectability of both the disks and the features of giant planet formation at early stage (i.e. gaps opened by the planets) in real observations, and the connection between the detected disk structure and the intrinsic properties of the system. We use real point spread functions of the Subaru telescope to convolve the images, in order to synthesize realistic images with the smallest spatial resolution and inner working angle which ground based instruments can provide at present. In the models without gaps, the effects of the disk depletion factor, mass, and flareness on the images are investigated, while for the models with a gap, we focus on the dependence of the detectability of the gap on the gap position, width, and depletion factor. Qualitatively, the more massive and more flared the disk is, the brighter the disk is. The gap is only visible when the disk is visible, and the deeper and wider the gap is, the larger the contrast level of the gap is.

Group A Streptococcus (GAS) commonly infects human skin and occasionally causes severe and life-threatening invasive diseases. The hyaluronan (HA) capsule of GAS has been proposed to protect GAS from host defense by mimicking endogenous HA, a large and abundant glycosaminoglycan in the skin. However, HA is degraded during tissue injury, and the functions of short-chain HA that is generated during infection have not been studied. To examine the impact of the molecular mass of HA on GAS infection, we established infection models in vitro and in vivo in which the size of HA was defined by enzymatic digestion or custom synthesis. We discovered that conversion of high molecular mass HA to low molecular mass HA facilitated GAS phagocytosis by macrophages and limited the severity of infection in mice. In contrast, native high molecular mass HA significantly impaired internalization by macrophages and increased GAS survival in murine blood. Thus, our data demonstrate that GAS virulence can be influenced by the size of HA derived from both the bacterium and host and suggest that high molecular mass HA facilitates GAS deep tissue infections, whereas the generation of short-chain HA can be protective.

Recent studies implicate the cohesin complex in transcriptional control, potentially through influences on long-distance communication between DNA elements. Animal models of Cornelia de Lange Syndrome (CdLS), the most common “cohesinopathy,” provide a unique opportunity to investigate both how cohesin regulates transcription, and the physiological consequences of disrupting that action. CdLS is most commonly caused by haploinsufficiency for NIPBL, a protein important for loading cohesin onto chromosomes, and individuals with CdLS frequently exhibit limb defects, particularly forelimb reductions of varying severity. Although Nipbl-deficient mice (Nipbl þ/ mice), display no gross limb abnormalities, we find that nipbl-deficient zebrafish exhibit severe reduction defects of the pectoral fins, the homologues of the mammalian forelimb. These defects are preceded by dysregulated expression of key developmental genes in the early limb (fin) bud, including fgfs in the apical ectodermal ridge; and shha, hand2, and hox genes in limb mesenchyme. Intriguingly, a strikingly similar pattern of gene expression changes can be detected in the limb buds of Nipbl-haploinsufficient mice, although the magnitude of gene expression changes is smaller. Limb bud-specific expression of Shh and Hox genes is known to be controlled by long-range enhancerpromoter interactions, and the pattern of changes in hox expression that occurs in Nipbl-deficient fin buds—characterized by downregulation of 5 0 hox genes and up-regulation of 3 0 hox genes—is consistent with the impairment of such long-range effects. Interestingly, knocking down expression of Med12—a subunit of the Mediator complex, which regulates promoter-enhancer communication and can co-localize with Nipbl on DNA—phenocopies morphological and transcriptional changes observed in Nipbldeficient fin buds. Moreover, partial reductions of Nipbl and Med12 interact synergistically, suggesting action in a common pathway. Overall, the data support the view that Nipbl and cohesin, most likely acting in concert with the Mediator complex, regulate limb-specific gene expression and limb development by influencing long-range chromosomal interactions, and suggest that these changes in expression in Nipbl-deficient limbs and fins are pathophysiologically significant in CdLS. Supported by NIH grant P01- HD052860 to ALC and ADL.

Cornelia de Lange Syndrome (CdLS) is the founding member of a class of multi-organ system birth defect syndromes termed cohesinopathies, named for the chromatin-associated protein complex cohesin, which mediates sister chromatid cohesion. Most cases of CdLS are caused by haploinsufficiency for Nipped-B-like (Nipbl), a highly conserved protein that facilitates cohesin loading. Consistent with recent evidence implicating cohesin and Nipbl in transcriptional regulation, both CdLS cell lines and tissues of Nipbl-deficient mice show changes in the expression of hundreds of genes. Nearly all such changes are modest, however-usually less than 1.5-fold-raising the intriguing possibility that, in CdLS, severe developmental defects result from the collective action of many otherwise innocuous perturbations. As a step toward testing this hypothesis, we developed a model of nipbl-deficiency in zebrafish, an organism in which we can quantitatively investigate the combinatorial effects of gene expression changes. After characterizing the structure and embryonic expression of the two zebrafish nipbl genes, we showed that morpholino knockdown of these genes produces a spectrum of specific heart and gut/visceral organ defects with similarities to those in CdLS. Analysis of nipbl morphants further revealed that, as early as gastrulation, expression of genes involved in endodermal differentiation (sox32, sox17, foxa2, and gata5) and left-right patterning (spaw, lefty2, and dnah9) is altered. Experimental manipulation of the levels of several such genes-using RNA injection or morpholino knockdown-implicated both additive and synergistic interactions in causing observed developmental defects. These findings support the view that birth defects in CdLS arise from collective effects of quantitative changes in gene expression. Interestingly, both the phenotypes and gene expression changes in nipbl morphants differed from those in mutants or morphants for genes encoding cohesin subunits, suggesting that the transcriptional functions of Nipbl cannot be ascribed simply to its role in cohesin loading.

我 々 は こ れ まで に、TGF 一βフ ァ ミ リーの 分泌 因子 で あ る Gdf11 や Activinβ B が 嗅覚上 皮 の 発 生 を負 に 制御す る こ とを見出 した 。 さ らに 、転 写因了一Foxg1 が TGF 一βフ ァ ミ リーの 分 泌 因 子 Gdfl1 の 活性制御 を通 じて 嗅覚上 皮 の 発 生 に 関与 す る こ と を、マ ウ ス の 遺伝学的 手 法 を用 い て 発 見 し た。こ れ らの 結 果 は 、Foxg1 と フ ォ リス タ チ ン （Fst）を介 した、Gdfl・1 の 「負の フ ィ ー ドバ ッ ク機構」の 適 切な制御が 、嗅覚上 皮 の 層構 造 形 成 （histogcnesis）お よ び 鼻甲介形成 （morphogcnesis ）の 両 方 に 重 要 で あ る が 、そ の 制 御 機構 に は 差 異が あ る こ とを示 して い る 。 / It has so far, it was found that TGF-β family of secreted factors and is Gdf11 and ActivinβB to control the negative occurrence of the olfactory epithelium. In addition, the transcription factor Foxg1 is to be involved in the development of the olfactory epithelium through active control of secreted factors Gdf11 of the TGF-β family, was discovered using genetic techniques in mice. These results, through the Foxg1 and follistatin (Fst), appropriate control of the "negative feedback mechanism" of Gdf11 is, important to both of the layer structure formation of the olfactory epithelium (histogenesis) and nasal turbinates formation (morphogenesis) although, it is shown that there are differences in the control mechanism.