This article deals with the way the themes of transmission and homosexuality intersect in E. M. Forster’s The Life to Come and Other Stories, a collection of short stories published posthumously in ...1972. First, it deals with the way in which the stories, which were written prior to the Sexual Offences Act 1967, play with transmission as a form of contagion which triggers moral panics throughout the stories. The article then moves on to study the question of inheritance and pays particular attention to the device of the will which does not only ensure the transmission of material goods but also serves as a tool to assert one’s subjectivity and identity. This shift is particularly important in the context of gay-themed texts since the late 19th century and early 20th century saw the constitution of a distinct homosexual identity. Finally, we will study the way the collection works toward the transmission of the memory of criminalisation in England and Wales.
Innate lymphoid cells (ILCs) have potent immunological functions in experimental conditions in mice, but their contributions to immunity in natural conditions in humans have remained unclear. We ...investigated the presence of ILCs in a cohort of patients with severe combined immunodeficiency (SCID). All ILC subsets were absent in patients with SCID who had mutation of the gene encoding the common γ-chain cytokine receptor subunit IL-2Rγ or the gene encoding the tyrosine kinase JAK3. T cell reconstitution was observed in patients with SCID after hematopoietic stem cell transplantation (HSCT), but the patients still had considerably fewer ILCs in the absence of myeloablation than did healthy control subjects, with the exception of rare cases of reconstitution of the ILC1 subset of ILCs. Notably, the ILC deficiencies observed were not associated with any particular susceptibility to disease, with follow-up extending from 7 years to 39 years after HSCT. We thus report here selective ILC deficiency in humans and show that ILCs might be dispensable in natural conditions, if T cells are present and B cell function is preserved.
Tissue-resident macrophages adapt to local signals within tissues to acquire specific functions. Neoplasia transforms the tissue, raising the question as to how the environmental perturbations ...contribute to tumor-associated macrophage (TAM) identity and functions. Combining single-cell RNA sequencing (scRNA-seq) with spatial localization of distinct TAM subsets by imaging, we discover that TAM transcriptomic programs follow two main differentiation paths according to their localization in the stroma or in the neoplastic epithelium of the mammary duct. Furthermore, this diversity is exclusively detected in a spontaneous tumor model and tracks the different tissue territories as well as the type of tumor lesion. These TAM subsets harbor distinct capacity to activate CD8+ T cells and phagocyte tumor cells, supporting that specific tumor regions, rather than defined activation states, are the major drivers of TAM plasticity and heterogeneity. The distinctions created here provide a framework to design cancer treatment targeting specific TAM niches.
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•TAMs differentiate according to their localization in situ•TAM heterogeneity is associated with resident TAM diversity prior to tumor development•Orthotopic tumor models negate TAM diversity•Similar heterogeneity is found in human breast TAMs
The origin of tumor-associated macrophage (TAM) heterogeneity is unclear. Laviron et al. show that TAM diversity is driven by the various tissue territories existing prior to tumor apparition and by the state of tumor malignancy. This provides a definition of TAM heterogeneity according to their spatial distribution in situ.
The establishment of separated pulmonary and systemic circulation in vertebrates, via cardiac outflow tract (OFT) septation, is a sensitive developmental process accounting for 10% of all congenital ...anomalies. Neural Crest Cells (NCC) colonising the heart condensate along the primitive endocardial tube and force its scission into two tubes. Here, we show that NCC aggregation progressively decreases along the OFT distal-proximal axis following a BMP signalling gradient. Dullard, a nuclear phosphatase, tunes the BMP gradient amplitude and prevents NCC premature condensation. Dullard maintains transcriptional programs providing NCC with mesenchymal traits. It attenuates the expression of the aggregation factor
and conversely promotes that of the epithelial-mesenchymal transition driver
. Altogether, Dullard-mediated fine-tuning of BMP signalling ensures the timed and progressive zipper-like closure of the OFT by the NCC and prevents the formation of a heart carrying the congenital abnormalities defining the tetralogy of Fallot.
A short G1 phase is a characteristic feature of mouse embryonic stem cells (ESCs). To determine if there is a causal relationship between G1 phase restriction and pluripotency, we made use of the ...Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) reporter system to FACS-sort ESCs in the different cell cycle phases. Hence, the G1 phase cells appeared to be more susceptible to differentiation, particularly when ESCs self-renewed in the naïve state of pluripotency. Transitions from ground to naïve, then from naïve to primed states of pluripotency were associated with increased durations of the G1 phase, and cyclin E-mediated alteration of the G1/S transition altered the balance between self-renewal and differentiation. LIF withdrawal resulted in a lengthening of the G1 phase in naïve ESCs, which occurred prior to the appearance of early lineage-specific markers, and could be reversed upon LIF supplementation. We concluded that the short G1 phase observed in murine ESCs was a determinant of naïve pluripotency and was partially under the control of LIF signaling.
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► We engineered mouse ES cells for live cell imaging of cell cycle progression. ► mESCs in the G1 phase have an increased susceptibility to differentiation. ► G1 phase duration varies according to the pluripotency state. ► LIF regulates the kinetics of G1 phase progression in naïve ES cells.
Innate lymphoid cells (ILC) are important players of early immune defenses in situations like lymphoid organogenesis or in case of immune response to inflammation, infection and cancer. Th1 and Th2 ...antagonism is crucial for the regulation of immune responses, however mechanisms are still unclear for ILC functions. ILC2 and NK cells were reported to be both involved in allergic airway diseases and were shown to be able to interplay in the regulation of the immune response. CXCR6 is a common chemokine receptor expressed by all ILC, and its deficiency affects ILC2 and ILC1/NK cell numbers and functions in lungs in both steady-state and inflammatory conditions. We determined that the absence of a specific ILC2 KLRG1
ST2
subset in CXCR6-deficient mice is probably dependent on CXCR6 for its recruitment to the lung under inflammation. We show that despite their decreased numbers, lung CXCR6-deficient ILC2 are even more activated cells producing large amount of type 2 cytokines that could drive eosinophilia. This is strongly associated to the decrease of the lung Th1 response in CXCR6-deficient mice.
T and innate lymphoid cells (ILCs) share some aspects of their developmental programs. However, although Notch signaling is strictly required for T cell development, it is dispensable for fetal ILC ...development. Constitutive activation of Notch signaling, at the common lymphoid progenitor stage, drives T cell development and abrogates ILC development by preventing Id2 expression. By combining single-cell transcriptomics and clonal culture strategies, we characterize two heterogeneous α4β7-expressing lymphoid progenitor compartments. αLP1 (Flt3+) still retains T cell potential and comprises the global ILC progenitor, while αLP2 (Flt3−) consists of ILC precursors that are primed toward the different ILC lineages. Only a subset of αLP2 precursors is sensitive to Notch signaling required for their proliferation. Our study identifies, in a refined manner, the diversity of transitional stages of ILC development, their transcriptional signatures, and their differential dependence on Notch signaling.
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•Global ILC progenitor and T precursors are found in the αLP1 compartment•αLP2 compartment is heterogeneously composed of primed ILC precursors•Notch signaling specifically acts on proliferation of an αLP2 ILC2 primed subset•Constitutive NICD expression drives T cell development and restrains Id2 expression
Molecular pathways and transcription factors involved in innate lymphoid cell (ILC) development are currently under intense investigation. Chea et al. now characterize different stages of ILC progenitors, from a global ILC progenitor (GILP) to committed ILC precursors, that are differentially sensitive to Notch signaling.
Greedy algorithms for NLP such as transition-based parsing are prone to error propagation. One way to overcome this problem is to allow the algorithm to backtrack and explore an alternative solution ...in cases where new evidence contradicts the solution explored so far. In order to implement such a behavior, we use reinforcement learning and let the algorithm backtrack in cases where such an action gets a better reward than continuing to explore the current solution. We test this idea on both POS tagging and dependency parsing and show that backtracking is an effective means to fight against error propagation.
Abstract
The use of artificial intelligence and algorithmic decision-making in public policy processes is influenced by a range of diverse drivers. This article provides a comprehensive view of 13 ...drivers and their interrelationships, identified through empirical findings from the taxation and social security domains in Belgium. These drivers are organized into five hierarchical layers that policy designers need to focus on when introducing advanced analytics in fraud detection: (a) trust layer, (b) interoperability layer, (c) perceived benefits layer, (d) data governance layer, and (e) digital governance layer. The layered approach enables a holistic view of assessing adoption challenges concerning new digital technologies. The research uses thematic analysis and interpretive structural modeling.
Innate lymphoid cells are present at mucosal sites and represent the first immune barrier against infections, but what contributes to their circulation and homing is still unclear. Using Rag2 −/− ...Cxcr6 Gfp/+ reporter mice, we assessed the expression and role of CXCR6 in the circulation of ILC precursors and their progeny. We identify CXCR6 expressing ILC precursors in the bone marrow and characterize their significant increase in CXCR6-deficient mice at steady state, indicating their partial retention in the bone marrow after CXCR6 ablation. Circulation was also impaired during embryonic life as fetal liver from CXCR6-deficient embryos displayed decreased numbers of ILC3 precursors. When injected, fetal CXCR6-deficient ILC3 precursors also fail to home and reconstitute ILC compartments in vivo. We show that adult intestinal ILC subsets have heterogeneous expression pattern of CXCR6, integrin α 4 β 7, CD62L, CD69, and CD44, with ILC1 and ILC3 being more likely tissue resident lymphocytes. Intestinal ILC subsets were unchanged in percentages and numbers in both mice. We demonstrate that the ILC frequency is maintained due to a significant increase of ILC peripheral proliferation, as well as an increased proliferation of the in situ ILC precursors to compensate their retention in the bone marrow.
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