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Cultural rights and justice : sustainable development, the arts and the body
\"This book provides an innovative contribution to the emerging field of culture and development through the lens of cultural rights, arguing in favour of a fruitful dialogue between human rights, development studies, critical cultural studies, and concerns about the protection and preservation of cultural diversity. It breaks with established approaches by introducing the themes of aesthetics, embodiment, narrative and peace studies into the field of culture and development, and in doing so, proposes both an expanded conception of cultural rights and a holistic vision of development that not only includes these elements in a central way, but which argues that genuine sustainability must include the cultural dimension, including the notion of cultural justice as recognition, protection and respect extended to the many expressions of human imagination in this world\"--Back cover.
Book
Dysmorphic neurons express markers of inhibitory glycinergic signaling in focal cortical dysplasia IIb
Focal cortical dysplasia (FCD) is a neurodevelopmental malformation that often manifests as medically refractory epilepsy. A key histological hallmark of FCD type II is the presence of cytomegalic dysmorphic neurons (CDNs), which are considered to be major contributors to cortical network hyperexcitability. However, the relatively low frequency of CDNs within resected lesions has challenged their unbiased molecular characterization. Here, we leverage deep learning approaches to objectively map key anatomical compartments of FCD IIb and guide regional spatial transcriptomic profiling. Using this approach, we generate an anatomical transcriptional catalog of type IIb FCD, and uncover non‐canonical markers of signaling and neurotransmitter pathways in CDNs that may serve as new therapeutic targets for this debilitating disorder. Deep learning tissue mapping can guide region of interest selection for spatial transcriptomic analyses. Using this method, a transcriptional catalogue of focal cortical dysplasia type IIb was generated, revealing enrichment for markers of inhibitory glycinergic signaling in cytomegalic dysmorphic neurons.
Journal Article
Cortical Dysplasia and the mTOR Pathway: How the Study of Human Brain Tissue Has Led to Insights into Epileptogenesis
Type II focal cortical dysplasia (FCD) is a neuropathological entity characterised by cortical dyslamination with the presence of dysmorphic neurons only (FCDIIA) or the presence of both dysmorphic neurons and balloon cells (FCDIIB). The year 2021 marks the 50th anniversary of the recognition of FCD as a cause of drug resistant epilepsy, and it is now the most common reason for epilepsy surgery. The causes of FCD remained unknown until relatively recently. The study of resected human FCD tissue using novel genomic technologies has led to remarkable advances in understanding the genetic basis of FCD. Mechanistic parallels have emerged between these non-neoplastic lesions and neoplastic disorders of cell growth and differentiation, especially through perturbations of the mammalian target of rapamycin (mTOR) signalling pathway. This narrative review presents the advances through which the aetiology of FCDII has been elucidated in chronological order, from recognition of an association between FCD and the mTOR pathway to the identification of somatic mosaicism within FCD tissue. We discuss the role of a two-hit mechanism, highlight current challenges and future directions in detecting somatic mosaicism in brain and discuss how knowledge of FCD may inform novel precision treatments of these focal epileptogenic malformations of human cortical development.
Journal Article
Research partnerships in early childhood education : teachers and researchers in collaboration
\"How can teachers deepen their understanding of their work? How can researchers make sure their work is grounded in and responsive to community needs? In this assemblage of rich examples of partnership research in early years education, Duncan and Conner set out how early childhood teachers and researchers can work in partnerships that benefit them both. Drawing on examples of successful partnerships from Canada, Australia, and New Zealand, they tell the stories of the successes, struggles, insights, and opportunities that come from working in such partnerships. Each chapter describes its own political, social, cultural and educational contexts, identifying the importance of complementary and reciprocal expertise required to solve educational puzzles. Through skillful analysis, this volume demonstrates how collaborative research on early childhood education results in gains for educators, researchers, and children alike\"-- Provided by publisher.
Book
Transcriptomic and morphologic vascular aberrations underlying FCDIIb etiology
Focal cortical dysplasia type II (FCDII) is a major cause of drug-resistant epilepsy, but genetic factors explain only some cases, suggesting other mechanisms. In this study, we conduct a molecular analysis of brain lesions and adjacent areas in FCDIIb patients. By analyzing over 217,506 single-nucleus transcriptional profiles from 15 individuals, we find significant changes in smooth muscle cells (SMCs) and astrocytes. We identify abnormal vascular malformations and a unique type of SMC that we call “Firework cells”, which migrate from blood vessels into the brain parenchyma and associate with VIM
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cells. These abnormalities create localized ischemic-hypoxic (I/H) microenvironments, as confirmed by clinical data, further impairing astrocyte function, activating the HIF-1α/mTOR/S6 pathway, and causing neuronal loss. Using zebrafish models, we demonstrate that vascular abnormalities resulting in I/H environments promote seizures. Our results highlight vascular malformations as a factor in FCDIIb pathogenesis, suggesting potential therapeutic avenues.
Focal cortical dysplasia type II causes epileptic seizures and is associated with various types of neuronal abnormalities. This study uses patient tissue transcriptomics and animal models to reveal that vascular malformations are a key part of the pathology by creating ischemic-hypoxic microenvironments.
Journal Article
Team human
\"Team Human is a manifesto--a fiery distillation of preeminent digital theorist Douglas Rushkoff's most urgent thoughts on civilization and human nature. In one hundred lean and incisive statements, he argues that we are essentially social creatures, and that we achieve our greatest aspirations when we work together--not as individuals. Yet today society is threatened by a vast antihuman infrastructure that undermines our ability to connect. Money, once a means of exchange, is now a means of exploitation; education, conceived as way to elevate the working class, has become another assembly line; and the internet has only further divided us into increasingly atomized and radicalized groups. Team Human delivers a call to arms. If we are to resist and survive these destructive forces, we must recognize that being human is a team sport. In Rushkoff's own words: \"Being social may be the whole point.\" Harnessing wide-ranging research on human evolution, biology, and psychology, Rushkoff shows that when we work together we realize greater happiness, productivity, and peace. If we can find the others who understand this fundamental truth and reassert our humanity--together--we can make the world a better place to be human.\"--Provided by publisher.
Book
Increased activation of the WNT pathway in brain tissue from patients with cortical dysplasia type IIb
Focal cortical dysplasia (FCD) is a malformation of cortical development characterized by a heterogeneous group of lesions with high epileptogenic activity. Somatic mutations in the mTOR pathway are the primary cause of cortical malformations (MCDs). Activation of the WNT pathway inhibits GSK3, which is a key inhibitor of mTOR; consequently, WNT activation is associated with increased activation of the mTOR pathway. Residual samples were obtained from the neocortex of five patients diagnosed with FCD type IIb who underwent surgery. For the control group, residual samples from the neocortex of 3 patients with temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) were used. The samples were used to evaluate relative gene expression levels, immunohistochemical characteristics, and the quantification of proteins related to the WNT pathway by Western blot. Gene expression analysis showed increased fold-changes in the genes LRP5, LRP6, DKK1, and DVL1. Immunohistochemistry analysis revealed that the FCD brain samples exhibited more staining for LRP6 compared to control brain tissue. All patients with FCD showed stronger staining for β-catenin. The increased gene expression of WNT pathway genes, combined with the intensified anti-LRP6 antibody staining and increased β-catenin staining, along with the reduced rate of β-catenin phosphorylation observed in patients with FCD, suggests a more pronounced activation of the WNT pathway.
Journal Article
Single-cell genotyping and transcriptomic profiling of mosaic focal cortical dysplasia
Focal cortical dysplasia type II (FCDII) is a cortical malformation causing refractory epilepsy. FCDII arises from developmental somatic activating mutations in mTOR pathway genes, leading to focal cortical dyslamination and abnormal cytomegalic cells. Which cell types carry pathogenic mutations and how they affect cell-type-specific transcriptional programs remain unknown. In the present study, we combined several single-nucleus genotyping and transcriptomics approaches with spatial resolution in surgical cortical specimens from patients with genetically mosaic FCDII. Mutations were detected in distinct cell types, including glutamatergic neurons and astrocytes, and a small fraction of mutated cells exhibited cytomegalic features. Moreover, we identified cell-type-specific transcriptional dysregulations in both mutated and nonmutated FCDII cells, including synapse- and neurodevelopment-related pathways, that may account for epilepsy and dysregulation of mitochondrial metabolism pathways in cytomegalic cells. Together, these findings reveal cell-autonomous and non-cell-autonomous features of FCDII that may be leveraged for precision medicine.
In this work, the authors performed a single-cell genotyping and transcriptomics analysis, revealing cell-type-specific and nonautonomous effects of mTOR pathway mutations in mosaic focal cortical dysplasia.
Journal Article