GATA3 mediates nonclassical β-catenin signaling in skeletal cell fate determination and ectopic chondrogenesis

Skeletal precursors are mesenchymal in origin and can give rise to distinct sublineages. Their lineage commitment is modulated by various signaling pathways. The importance of Wnt signaling in skeletal lineage commitment has been implicated by the study of β-catenin-deficient mouse models. Ectopic chondrogenesis caused by the loss of β-catenin leads to a long-standing belief in canonical Wnt signaling that determines skeletal cell fate. As β-catenin has other functions, it remains unclear whether skeletogenic lineage commitment is solely orchestrated by canonical Wnt signaling. The study of the Wnt secretion regulator Gpr177/Wntless also raises concerns about current knowledge. Here, we show that skeletal cell fate is determined by β-catenin but independent of LEF/TCF transcription. Genomic and bioinformatic analyses further identify GATA3 as a mediator for the alternative signaling effects. GATA3 alone is sufficient to promote ectopic cartilage formation, demonstrating its essential role in mediating nonclassical β-catenin signaling in skeletogenic lineage specification

β-catenin/cyclin D1 mediated development of suture mesenchyme in calvarial morphogenesis

<p>Abstract</p> <p>Background</p> <p>Mouse genetic study has demonstrated that Axin2 is essential for calvarial development and disease. Haploid deficiency of β-catenin alleviates the calvarial phenotype caused by Axin2 deficiency. This loss-of-function study provides evidence for the requirement of β-catenin in exerting the downstream effects of Axin2.</p> <p>Results</p> <p>Here we utilize a gain-of-function analysis to further assess the role of β-catenin. A transgenic expression system permitting conditional activation of β-catenin in a spatiotemporal specific manner has been developed. Aberrant stimulation of β-catenin leads to increases in expansion of skeletogenic precursors and the enhancement of bone ossification reminiscent to the loss of Axin2. The constitutively active signal promotes specification of osteoprogenitors, but prevents their maturation into terminally differentiated osteoblasts, along the osteoblast lineage. However, the prevention does not interfere with bone synthesis, suggesting that mineralization occurs without the presence of mature osteoblasts. β-catenin signaling apparently plays a key role in suture development through modulation of calvarial morphogenetic signaling pathways. Furthermore, genetic inactivation of the β-catenin transcriptional target, cyclin D1, impairs expansion of the skeletogenic precursors contributing to deficiencies in calvarial ossification. There is a specific requirement for cyclin D1 in populating osteoprogenitor cell types at various developmental stages.</p> <p>Conclusion</p> <p>These findings advance our knowledge base of Wnt signaling in calvarial morphogenesis, suggesting a key regulatory pathway of Axin2/β-catenin/cyclin D1 in development of the suture mesenchyme.</p

Correlation between magnifying narrow band imaging and histopathology in gastric protruding/or polypoid lesions: a pilot feasibility trial

<p>Abstract</p> <p>Background</p> <p>Several study showed usefulness of microscopic capillaries, seen by magnifying narrow band imaging (NBI) endoscopy for predicting histopathology among superficial depressed or flat elevated gastric neoplasia (GN). Here we assessed the diagnostic efficacy of magnifying NBI for predicting histopathology among gastric protruding/or polypoid lesions.</p> <p>Methods</p> <p>Using endoscopic pictures of magnifying NBI from 95 protruding/or polypoid lesions (19 fundic gland polyps: FGP, 47 hyperplastic polyps: HP, and 29 GN), fine mucosal patterns were classified into four categories: small round, prolonged, villous or ridge, and unclear patterns, and micro vascular patterns were classified into five categories: honey comb, dense vascular, fine net work, core vascular, and unclear patterns.</p> <p>Results</p> <p>Most suggestive micro vascular patterns for predicting FGP, and HP were honeycomb (sensitivity 94.7%, specificity 97.4%), and dense vascular patterns (sensitivity 93.6%, specificity 91.6%), respectively. Fine net work, core vascular, and unclear patterns presented higher specificity (97%, 100%, and 100%) for predicting GN, and diagnostic efficacy of combined of those patterns was favorable (sensitivity 86.2%, specificity 97.0%).</p> <p>Conclusion</p> <p>Micro vascular patterns by using magnifying NBI provides meaningful information for predicting the histopathology of gastric protruding/or polypoid lesions.</p

Effects of time-compressed speech training on multiple functional and structural neural mechanisms involving the left superior temporal gyrus

Time-compressed speech is an artificial form of rapidly presented speech. Training with time-compressed speech (TCSSL) in a second language leads to adaptation toward TCSSL. Here, we newly investigated the effects of 4 weeks of training with TCSSL on diverse cognitive functions and neural systems using the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), resting-state functional connectivity (RSFC) with the left superior temporal gyrus (STG), fractional anisotropy (FA), and regional gray matter volume (rGMV) of young adults by magnetic resonance imaging. There were no significant differences in change of performance of measures of cognitive functions or second language skills after training with TCSSL compared with that of the active control group. However, compared with the active control group, training with TCSSL was associated with increased fALFF, RSFC, and FA and decreased rGMV involving areas in the left STG. These results lacked evidence of a far transfer effect of time-compressed speech training on a wide range of cognitive functions and second language skills in young adults. However, these results demonstrated effects of time-compressed speech training on gray and white matter structures as well as on resting-state intrinsic activity and connectivity involving the left STG, which plays a key role in listening comprehension

Effects of time-compressed speech training on multiple functional and structural neural mechanisms involving the left superior temporal gyrus

Time-compressed speech is an artificial form of rapidly presented speech. Training with time compressed speech in a second language leads to adaptation toward time-compressed speech in a second language and toward time compressed speech in different languages. However, the effects of training with time-compressed speech of a second language (TCSSL) on diverse cognitive functions and neural mechanisms beyond time compressed speech-related activation are unknown. We investigated the effects of 4 weeks of training with TCSSL on the fractional amplitude of spontaneous low-frequency fluctuations (fALFF) of 0.01–0.08 Hz, resting-state functional connectivity (RSFC) with the left superior temporal gyrus (STG), fractional anisotropy (FA), and regional gray matter volume (rGMV) of young adults by magnetic resonance imaging. There were no significant differences in change of performance of measures of cognitive functions or second language skills after training with TCSSL compared with that of the active control group. However, compared with the active control group, training with TCSSL was associated with increased fALFF, RSFC, and FA and decreased rGMV involving areas in the left STG. These results lacked evidence of a far transfer effect of time compressed speech training on a wide range of cognitive functions and second language skills in young adults. However, these results demonstrated effects of time compressed speech training on gray and white matter structures as well as on resting-state intrinsic activity and connectivity involving the left STG, which plays a key role in listening comprehension

Lenticular nucleus correlates of general self-efficacy in young adults

General self-efficacy (GSE) is an important factor in education, social participation, and medical treatment. However, the only study that has investigated the direct association between GSE and a neural correlate did not identify specific brain regions, rather only assessed brain structures, and included older adult subjects. GSE is related to motivation, physical activity, learning, the willingness to initiate behaviour and expend effort, and adjustment. Thus, it was hypothesized in the present study that the neural correlates of GSE might be related to changes in the basal ganglia, which is a region related to the abovementioned self-efficacy factors. This study aimed to identify the brain structures associated with GSE in healthy young adults (n = 1204, 691 males and 513 females, age 20.7 ± 1.8 years) using regional grey matter density and volume (rGMD and rGMV), fractional anisotropy (FA) and mean diffusivity (MD) analyses of magnetic resonance imaging (MRI) data. The findings showed that scores on the GSE Scale (GSES) were associated with a lower MD value in regions from the right putamen to the globus pallidum; however, there were no significant association between GSES scores and regional brain structures using the other analyses (rGMD, rGMV, and FA). Thus, the present findings indicated that the lenticular nucleus is a neural correlate of GSE

Limited Regeneration of Adult Salivary Glands after Severe Injury Involves Cellular Plasticity

Summary: In the adult salivary glands, the origin of replacement and regenerated acinar cells remains unclear. Although many reports describe the identification of stem cells in adult salivary glands, we have shown that differentiated acinar cells can be maintained and regenerated through self-duplication. Here, we have used genetic mouse models to further investigate acinar cell replacement and regeneration during homeostasis and after injury. Under normal conditions or after duct ligation, replacement of duct and acinar cells occurs through lineage-restricted progenitors. In contrast, after irradiation, in vivo lineage tracing shows that acinar, as well as duct, cells contribute to acinar cell regeneration, revealing that cellular plasticity is involved in salivary gland repair. Our results also indicate that even after radiation damage, several cell populations have regenerative potential for restoring salivary gland function. : Using in vivo lineage tracing, Weng et al. demonstrate that salivary gland acinar and duct lineages are maintained separately under homeostasis and after duct ligation, but after irradiation, both duct and acinar cells generate acini. This indicates that several cell populations have the potential to restore salivary gland function

Mitotic-spindle associated genes are among the common genes responding to ionizing radiation

Accelerated ion particle with higher LET (linear energy transfer) is promising for the treatment of certain kinds of malignancy. Molecular basis of its advantage over conventional radiotherapy, however, has not been clarified. Using HiCEP (high-coverage expression profiling), we compared gene expression profiles in the normal diploid human fibroblasts (HFLIII) irradiated with three types of clinically relevant radiation at 2Gy; X-ray (0.9 Gy/min), and carbon ion beam of either low (13 keV/micro-m) or high (70 keV/micro-m) LET. RNA was extracted at 2, 4 and 6 hr later and the expression levels for approximate 16,000 transcripts were compared between samples irradiated and mock-irradiated. Through all the nine comparison analyses, we selected 11 IR-responsive genes (signatures), which included upregulated transcripts, (BTG2, ATF3, CDKN1Aetc.) and also downregulated genes, CCNF (Cyclin F) and ASPM (abnormal spindle-like microcephaly associated). Further comparison study demonstrated that carbon particles of higher LET prolong the expression of earlier-responding genes particularly among those which are known to be upregulated under p53 control. Since it was documented that both CCNF and ASPM are required for normal mitotic-spindle formation in somatic cells, our present results would provide a novel insight into the carbon ion beams causing the significant reduction in these spindle-mitotic proteins on DNA damage response.14 th ICR