Significance: Somatic mutations converting glycine 34 of histone H3 (H3G34) to a large side chain-containing residue (e.g., arginine, valine) cause pediatric gliomas; however, the mechanism of this is unknown. Because H3K36me3 is involved in mismatch repair (MMR) by recruiting MMR protein MutSα to chromatin, we hypothesized that H3G34R/V mutations block H3K36’s interactions with both MutSα and H3K36-specific methyltransferases, leading to MMR deficiency. We show here that this is indeed the case. Structural analysis revealed that H3G34 resides in a narrow substrate channel of the H3K36 trimethyltransferase SETD2. Thus, H3G34R/V mutations impair the catalytic activity of SETD2. H3G34R/V mutations also block the H3K36me3–MutSα interaction. Cells harboring H3G34R/V mutations display a mutator phenotype. This study reveals the molecular basis of how H3G34 mutations cause pediatric gliomas.

Histone H3 trimethylation at lysine 36 (H3K36me3) is an important histone mark involved in both transcription elongation and DNA mismatch repair (MMR). It is known that H3K36me3 recruits the mismatch-recognition protein MutSα to replicating chromatin via its physical interaction with MutSα's PWWP domain, but the exact role of H3K36me3 in transcription is undefined. Using ChIP combined with whole-genome DNA sequencing analysis, we demonstrate here that H3K36me3, together with MutSα, is involved in protecting against mutation, preferentially in actively transcribed genomic regions. We found that H3K36me3 and MutSα are much more co-enriched in exons and actively transcribed regions than in introns and nontranscribed regions. The H3K36me3-MutSα co-enrichment correlated with a much lower mutation frequency in exons and actively transcribed regions than in introns and nontranscribed regions. Correspondingly, depleting H3K36me3 or disrupting the H3K36me3-MutSα interaction elevated the spontaneous mutation frequency in actively transcribed genes, but it had little influence on the mutation frequency in nontranscribed or transcriptionally inactive regions. Similarly, H2O2-induced mutations, which mainly cause base oxidations, preferentially occurred in actively transcribed genes in MMR-deficient cells. The data presented here suggest that H3K36me3-mediated MMR preferentially safeguards actively transcribed genes not only during replication by efficiently correcting mispairs in early replicating chromatin but also during transcription by directly or indirectly removing DNA lesions associated with a persistently open chromatin structure.

The design and optimization of urban form has always been a hot topic in urban planning and development research. Besides, the creation of continuous vitality in urban areas is of critical importance in the development of urbanization. However, due to the lack of data, it is difficult to measure the effects of urban form on neighborhood vibrancy. Additionally, no uniform conclusion has been drawn regarding to what degree urban form can contribute to neighborhood vibrancy. Taking advantage of emerging new data sources, the depth and breadth of related research can now be improved. Therefore, this paper uses high-precision positioning social media check-in data to approximate the vibrancy of 658 neighborhoods, and uses a geographical information system (GIS) to quantitatively measure the urban form indicators in the central area of Chengdu City, China. A quantitative exploration and analysis of the relationships between neighborhood vibrancy and urban form is conducted. The results of three regression models considering different explanatory variables show that socio-economic factors account for approximately 23% of neighborhood vibrancy. In addition, the correlation between the shape characteristics of a neighborhood and the vibrancy is weak. However, when the inner urban form indicators of neighborhoods are introduced into the regression model, the goodness of fit (R²) is nearly doubled. This finding indicates that strong associations exist between urban form and neighborhood vibrancy. Specifically, building density and functional diversity are positively correlated with neighborhood vibrancy. Unlike existing studies, this study finds that the road network within the neighborhood plays a positive role in the creation of neighborhood vibrancy. However, the impact of a road density indicator is not as powerful as the impacts of building density and functional diversity. This research can help urban designers to better design urban environments.

In this study, we aim to understand the impact of land use on the urban heat island (UHI) effect across an urban area. Considering the case study of Wuhan, China, land use factors and land surface temperatures (LSTs) of 589 planning management units were quantified in order to identify the spatial autocorrelation of LST, which indicated that a traditional regression would be invalid. By investigating the relationships between land use factors and the LST in summer, based on spatial regression models including the spatial lag model and the spatial error model, four conclusions were derived. First, the spatial error model effectively explains the relationships between LST and land use factors. Second, the impact on LST of the percentage of industrial areas is significant even though the impacts of land cover and building-group morphology indicators are combined, indicating that anthropogenic heat emission of industrial production contributes to high LSTs. Third, the relationship between the percentage of commercial area and LST is significant in the Pearson correlation analysis and traditional regression models, while not significant in spatial error model, suggesting that the urban heat environment of a commercial area is determined by the land use factors of the surrounding area. Fourth, the UHI effect in industrial and commercial areas could be precisely mitigated by not locating industrial areas beside residential areas, and setting up buffer zones between commercial areas and surrounding traditional residential areas. Overall, the results of this study innovatively deepen the understanding of the impact of the percentage of different urban land use types on the urban heat environment at the scale of planning management units, which is conducive to formulating precise regulation measures for mitigating UHI effects and improving public health.

Since the founding of the country, China’s urban–rural relations have experienced four stages: differentiation, opposition, coordination, and equivalence. The scope of rural research has expanded from individual villages to group relations, and the research content also tends to the urban–rural integration trend of factor flow. In the context of New Urbanization and the Rural Revitalization Strategies, urban–rural integration is an important starting point to solve urban–rural contradictions, and the metropolitan area is an important spatial carrier to achieving urban–rural integration. Based on investigating the key issues of urban–rural integration and metropolitan governance, this paper constructs a “place function” cognitive framework of urban–rural space in the metropolitan area, and takes Wuhan metropolitan area with its dense rural distribution as an example to recognize the urban–rural spatial characteristics of the metropolitan area scale from six dimensions: spatial structure, land use, settlement distribution, scenic spots, agricultural enterprises, and service facilities. Then, it proposes a spatial development model of the Wuhan metropolitan area of the “point axis structure-, functional area-, resilient network”, and further explores the urban–rural integration path of “planning guidance, policy promotion, and spatial support”.