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This essay traces the evolution of children's geographies as a concept through three phases. First, in the early 1970s as a beginning impression influenced heavily by developmental and environmental psychology. Second, beginning around 1990, children's geographies cohered politically as geographers focused on young people's identity through feminism and Marxism, and global policy initiatives on children's rights. The third phase, covering the last couple of decades, coming from issues of political identity, challenges what we think we know about young people and their geographies, and also advocates a set of loose theories about the ways young people create and re-create spaces and themselves. Cognate disciplines coming to geography for insights about children and their worlds characterize this current phase. To offset this seeming linear progression the essay also notes an involution of the concept that defies clear categories and sequences, but suggests the fluidity of tensions and accommodations that comprises children's geographies.

The case of Slovenia's erased minority populations (Izbrisani) is cited as one of the worst human rights abuses in contemporary Europe. While engaging debates on the nation-state and neoliberalism, this article discusses the struggles of Izbrisani youth from 1992 to the present day through a consideration of the spatial effects of erasure, including trauma to families forced apart and young people locked in place. Theoretical insights are drawn from Agamben's ideas about bare life, Rancière's politicization of aesthetics, and Žižek's notion of radical ethical acts, which respectively provide lenses for understanding Izbrisani youth privations, awakenings, and transformations.

The eviction of families from historically nationalized and recently restituted houses in Romania is tied in complicated ways to postsocialist transitional justice policies. Delayed enactment of restitution legislation and inconsistent application leave families, and neglected houses, in a precarious state. As families remain in place, they create a politics that pushes against dispossession. Evidence of this push comes from a study of Roma families, who are arguably the most marginalized of Romania's low-income peoples. Theoretically, we draw on Butler and Athanasiou's understanding of precarity and dispossession and Askins's emotional citizenry, from which we find a glimmer of hope in the everyday performance of the political among threatened families.

In March 2013, several thousand delegates at China's National People's Congress voted to approve the environmentally sensitive and authoritarian Xi Jinping as president. This portended dramatic changes in environmental policies, not least of which was an offsetting of top-down development-at-all-costs dogma with a new official orthodoxy focused on a sustainable and circular economy, with inclusive and more rounded growth. This article is part of a long-term project (2008-2018) in Fanjingshan National Nature Reserve in Guizhou Province that took place as the political scene in Beijing shifted. The larger project is about human-environment dynamics and complexities focusing on the preservation of snub-nosed golden monkey habitat and the implementation of top-down grain-to-green and national forest conservation programs. This article is about the contexts of two development projects, one in the reserve and one just outside of it, with very different outcomes. Drawing on the work of Arturo Escobar, Rosi Braidotti, and Xiaobo Su, we argue for development in a time and place of rapid change as if marginalized farmers and their families mattered and the possibility of sustainable ethics with a locatable politics. The article elaborates the potency of this kind of sustainability through the stories of families living on Fanjingshan Reserve in the midst of (1) authoritarian environmental policy proclamations from Beijing and (2) boisterous local development. Key Words: China, development, sustainability.

Mammalian chromosomes fold into arrays of megabase‐sized topologically associating domains (TADs), which are arranged into compartments spanning multiple megabases of genomic DNA. TADs have internal substructures that are often cell type specific, but their higher‐order organization remains elusive. Here, we investigate TAD higher‐order interactions with Hi‐C through neuronal differentiation and show that they form a hierarchy of domains‐within‐domains (metaTADs) extending across genomic scales up to the range of entire chromosomes. We find that TAD interactions are well captured by tree‐like, hierarchical structures irrespective of cell type. metaTAD tree structures correlate with genetic, epigenomic and expression features, and structural tree rearrangements during differentiation are linked to transcriptional state changes. Using polymer modelling, we demonstrate that hierarchical folding promotes efficient chromatin packaging without the loss of contact specificity, highlighting a role far beyond the simple need for packing efficiency. Synopsis Genome‐wide mapping of chromatin architecture reveals a hierarchical folding of chromatin that involves higher‐order domains interactions across the whole chromosomes, reflects epigenomic features and reorganizes upon differentiation‐induced gene expression changes. Chromatin architecture is mapped genome‐wide using Hi‐C and a neuronal differentiation model from mESC to post‐mitotic neurons. Mammalian chromosomes fold hierarchically in a manner that reflects epigenomic features and involves higher‐order domains (metaTADs) up to the chromosome scale. metaTAD topologies are relatively conserved through differentiation, and their reorganization is related to gene expression changes. Polymer modelling shows that hierarchical chromatin folding promotes efficient packaging without the loss of contact specificity. Graphical Abstract Genome‐wide mapping of chromatin architecture reveals a hierarchical folding of chromatin that involves higher‐order domains interactions across the whole chromosomes, reflects epigenomic features and reorganizes upon differentiation‐induced gene expression changes.

Autophagy is a finely orchestrated process required for the lysosomal degradation of cytosolic components. The final degradation step is essential for clearing autophagic cargo and recycling macromolecules. Using a CRISPR/Cas9-based screen, we identify RNAseK, a highly conserved transmembrane protein, as a regulator of autophagosome degradation. Analyses of RNAseK knockout cells reveal that, while autophagosome maturation is intact, cargo degradation is severely disrupted. Importantly, lysosomal protease activity and acidification remain intact in the absence of RNAseK suggesting a specificity to autolysosome degradation. Analyses of lysosome fractions show reduced levels of a subset of hydrolases in the absence of RNAseK. Of these, the knockdown of PLD3 leads to a defect in autophagosome clearance. Furthermore, the lysosomal fraction of RNAseK-depleted cells exhibits an accumulation of the ESCRT-III complex component, VPS4a, which is required for the lysosomal targeting of PLD3. Altogether, here we identify a lysosomal hydrolase delivery pathway required for efficient autolysosome degradation. The degradation of inner autophagosomal membranes remains poorly understood. Here, Makar et al. show that RNAseK is involved in a lysosomal hydrolase delivery pathway that contributes to autophagosomal membrane degradation.

Activated hepatic stellate cells (aHSCs) orchestrate scarring during liver injury, with putative quiescent precursor mesodermal derivation. Here we use lineage-tracing from development, through adult homoeostasis, to fibrosis, to define morphologically and transcriptionally discreet subpopulations of aHSCs by expression of WT1 , a transcription factor controlling morphological transitions in organogenesis and adult homoeostasis. Two distinct populations of aHSCs express WT1 after injury, and both re-engage a transcriptional signature reflecting embryonic mesothelial origin of their discreet quiescent adult precursor. WT1 -deletion enhances fibrogenesis after injury, through upregulated Wnt-signalling and modulation of genes central to matrix persistence in aHSCs, and augmentation of myofibroblastic transition. The mesothelial-derived lineage demonstrates punctuated phenotypic plasticity through bidirectional mesothelial-mesenchymal transitions. Our findings demonstrate functional heterogeneity of adult scar-orchestrating cells that can be whole-life traced back through specific quiescent adult precursors to differential origin in development, and define WT1 as a paradoxical regulator of aHSCs induced by injury but suppressing scarring. Activated hepatic stellate cells of putative mesodermal origin orchestrate scarring during injury. Here, the authors define a discrete morphologically plastic lineage of embryonic mesothelial-derived scar-orchestrating cells, through a distinct quiescent adult precursor, defined and paradoxically inhibited by WT1.

Deciphering the structural variation across tumour genomes is crucial to determine the events driving tumour progression and better understand tumour adaptation and evolution. High grade serous ovarian cancer (HGSOC) is an exemplar tumour type showing extreme, but poorly characterised structural diversity. Here, we comprehensively describe the mutational landscape driving HGSOC, exploiting a large (N = 324), deeply whole genome sequenced dataset. We reveal two divergent evolutionary trajectories, affecting patient survival and involving differing genomic environments. One involves homologous recombination repair deficiency (HRD) while the other is dominated by whole genome duplication (WGD) with frequent chromothripsis, breakage-fusion-bridges and extra-chromosomal DNA. These trajectories contribute to structural variation hotspots, containing candidate driver genes with significantly altered expression. While structural variation predominantly drives tumorigenesis, we find high mtDNA mutation loads associated with shorter patient survival. We show that a combination of mutations in the mitochondrial and nuclear genomes impact prognosis, suggesting strategies for patient stratification. Tumour evolution and heterogeneity in high grade serous ovarian cancer (HGSOC) remains poorly characterised. Here, the authors investigate the genomic landscape of HGSOC and reveal two distinct evolutionary trajectories associated with clinical outcomes.

Tumour cell plasticity is a major barrier to the efficacy of targeted cancer therapies but the mechanisms that mediate it are poorly understood. Here, we identify dysregulated RNA splicing as a key driver of tumour cell dedifferentiation in colorectal cancer (CRC). We find that Apc -deficient CRC cells have dysregulated RNA splicing machinery and exhibit global rewiring of RNA splicing. We show that the splicing factor SRSF1 controls the plasticity of tumour cells by controlling Kras splicing and is required for CRC invasion in a mouse model of carcinogenesis. SRSF1 expression maintains stemness in human CRC organoids and correlates with cancer stem cell marker expression in human tumours. Crucially, partial genetic downregulation of Srsf1 does not detrimentally affect normal tissue homeostasis, demonstrating that tumour cell plasticity can be differentially targeted. Thus, our findings link dysregulation of the RNA splicing machinery and control of tumour cell plasticity. The influence of mRNA splicing on colon cancer development and progression is unclear. In this study, the authors demonstrate that the SRSF1 splicing factor is essential to sustain the stem cell phenotype of WNT-activated colorectal cancers.