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1.
Hist Human Sci ; 33(5): 110-137, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33304032

ABSTRACT

A conception of the idiotic mind was used to substantiate late 19th-century theories of mental evolution. A new school of animal/comparative psychologists attempted from the 1870s to demonstrate that evolution was a mental as well as a physical process. This intellectual enterprise necessitated the closure, or narrowing, of the 'consciousness gap' between human and animal species. A concept of a quasi-non-conscious human mind, set against conscious intention and ability in higher animals, provided an explanatory framework for the human-animal continuum and the evolution of consciousness. The article addresses a significant lacuna in the historiographies of intellectual disability, animal science, and evolutionary psychology, where the application of a conception of human idiocy to advance theories of consciousness evolution has not hitherto been explored. These ideas retain contemporary resonance in ethology and cognitive psychology, and in the theory of 'speciesism', outlined by Peter Singer in Animal Liberation (1975), which claims that equal consideration of interests is not arbitrarily restricted to members of the human species, and advocates euthanasia of intellectually disabled human infants. Speciesism remains at the core of animal rights activism today. The article also explores the influence of the idea of the semi-evolved idiot mind in late-Victorian anthropology and neuroscience. These ideas operated in a separate intellectual sphere to eugenic thought. They were (and remain) deeply influential, and were at the heart of the idea of the moral idiot or imbecile, targeted in the 1913 Mental Deficiency Act, as well as in 20th-century animal and human consciousness theory.

2.
Nat Commun ; 11(1): 3677, 2020 07 22.
Article in English | MEDLINE | ID: mdl-32699279

ABSTRACT

Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+ follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients.


Subject(s)
B-Lymphocytes/immunology , Cellular Microenvironment/immunology , Chemokine CXCL13/metabolism , Dendritic Cells, Follicular/immunology , Adaptive Immunity , Animals , B-Lymphocytes/cytology , B-Lymphocytes/metabolism , Cathepsin B/genetics , Cathepsin B/metabolism , Cell Line , Chemokine CXCL13/immunology , Computer Simulation , Dendritic Cells, Follicular/cytology , Dendritic Cells, Follicular/metabolism , Extracellular Matrix/metabolism , Humans , Mice , Mice, Knockout , Microscopy, Fluorescence , Models, Biological , Palatine Tonsil/cytology , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , Stromal Cells/immunology , Stromal Cells/metabolism
3.
Adv Exp Med Biol ; 915: 329-46, 2016.
Article in English | MEDLINE | ID: mdl-27193552

ABSTRACT

Immune responses occur as a result of stochastic interactions between a plethora of different cell types and molecules that regulate the migration and function of innate and adaptive immune cells to drive protection from pathogen infection. The trafficking of immune cells into peripheral tissues during inflammation and then subsequent migration to draining lymphoid tissues has been quantitated using radiolabelled immune cells over 40 years ago. However, how these processes lead to efficient immune responses was unclear. Advances in physics (multi-photon), chemistry (probes) and biology (animal models) have provided immunologists with specialized tools to quantify the molecular and cellular mechanisms driving immune function in lymphoid tissues through directly visualising cellular behaviours in 3-dimensions over time. Through the temporal and spatial resolution of multi-photon confocal microscopy immunologists have developed new insights into normal immune homeostasis, host responses to pathogens, anti-tumour immune responses and processes driving development of autoimmune pathologies, by the quantification of the interactions and cellular migration involved in adaptive immune responses. Advances in deep tissue imaging, including new fluorescent proteins, increased resolution, speed of image acquisition, sensitivity, number of signals and improved data analysis techniques have provided unprecedented capacity to quantify immune responses at the single cell level. This quantitative information has facilitated development of high-fidelity mathematical and computational models of immune function. Together this approach is providing new mechanistic understanding of immune responses and new insights into how immune modulators work. Advances in biophysics have therefore revolutionised our understanding of immune function, directly impacting on the development of next generation immunotherapies and vaccines, and is providing the quantitative basis for emerging technology of simulation-guided experimentation and immunotherapeutic design.


Subject(s)
Adaptive Immunity , Lymph Nodes/immunology , Molecular Imaging , Animals , Biomarkers/metabolism , Cell Communication , Cell Movement , Diffusion of Innovation , Forecasting , History, 20th Century , History, 21st Century , Humans , Imaging, Three-Dimensional , Lymph Nodes/metabolism , Lymph Nodes/pathology , Microscopy, Fluorescence, Multiphoton , Molecular Imaging/history , Molecular Imaging/methods , Molecular Imaging/trends , Signal Transduction , Time Factors
4.
Int J Dev Disabil ; 61(2): 107-112, 2015 Mar.
Article in English | MEDLINE | ID: mdl-28191310

ABSTRACT

This paper critically examines the term 'community' as applied to people with intellectual disabilities over time and aims to describe its shifting conceptualisation from the eighteenth century to the present day. Unpublished documentary sources from Old Bailey criminal trials in the eighteenth century, the Earlswood Idiot asylum in the mid-nineteenth-century and early-twentieth-century government reports have been used to explore historical changes in the concept of community. The word community is historically contingent both in its past and present uses. Its meaning has been adapted to strengthen and justify professional claims to own, treat and manage people with intellectual disabilities. Inclusion and community acceptance were normative in the eighteenth century. In later medicalized institutionalization programmes the meaning of community was subverted to endorse and vindicate professional claims. It has been further adapted since deinstitutionalization to support contemporary claims for the social model of community inclusion. Today's language of inclusion emanates from these historical conceptual shifts, masking a set of unconscious assumptions and meanings attached to the status of intellectually disabled people. The modern concept of community is based on an assumption that people with intellectual disabilities have always been excluded. In the collective memory, it has been forgotten that they were, before the asylum, natural members of community embedded within social, economic, and familial networks. It is communities themselves that must adapt and remodel rather than trying to remodel those people they originally excluded.

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