The Influence of Microbial Metabolites in the Gastrointestinal Microenvironment on Anticancer Immunity

The gastrointestinal (GI) tumour microenvironment is characterised by its unique colonisation with bacteria that are estimated to match the total number of cells in our body. It is becoming increasingly clear that the microbiome and its metabolites are important orchestrators of local and systemic immune responses, anticancer immunity and the host response to cancer therapy. Apart from their role as an energy source, metabolites have been shown to modulate inflammation, immune cell function and cancer cell survival. The polarisation of immune cell subsets by microbial metabolites towards either pro- or antitumorigenic functions strongly affects cancer progression and outcomes. In this chapter, we will discuss the link between microbial metabolites in the GI tumour microenvironment, anticancer immune responses and cancer progression

Vibrational dynamics of confined granular material

By means of two-dimensional contact dynamics simulations, we analyze the vibrational dynamics of a confined granular layer in response to harmonic forcing. We use irregular polygonal grains allowing for strong variability of solid fraction. The system involves a jammed state separating passive (loading) and active (unloading) states. We show that an approximate expression of the packing resistance force as a function of the displacement of the free retaining wall from the jamming position provides a good description of the dynamics. We study in detail the scaling of displacements and velocities with loading parameters. In particular, we find that, for a wide range of frequencies, the data collapse by scaling the displacements with the inverse square of frequency, the inverse of the force amplitude and the square of gravity. Interestingly, compaction occurs during the extension of the packing, followed by decompaction in the contraction phase. We show that the mean compaction rate increases linearly with frequency up to a characteristic frequency and then it declines in inverse proportion to frequency. The characteristic frequency is interpreted in terms of the time required for the relaxation of the packing through collective grain rearrangements between two equilibrium states

Force transmission in a packing of pentagonal particles

We perform a detailed analysis of the contact force network in a dense confined packing of pentagonal particles simulated by means of the contact dynamics method. The effect of particle shape is evidenced by comparing the data from pentagon packing and from a packing with identical characteristics except for the circular shape of the particles. A counterintuitive finding of this work is that, under steady shearing, the pentagon packing develops a lower structural anisotropy than the disk packing. We show that this weakness is compensated by a higher force anisotropy, leading to enhanced shear strength of the pentagon packing. We revisit "strong" and "weak" force networks in the pentagon packing, but our simulation data provide also evidence for a large class of "very weak" forces carried mainly by vertex-to-edge contacts. The strong force chains are mostly composed of edge-to-edge contacts with a marked zig-zag aspect and a decreasing exponential probability distribution as in a disk packing

Late-stage MC38 tumours recapitulate features of human colorectal cancer – implications for appropriate timepoint selection in preclinical studies

Anti-tumour T cell responses play a crucial role in controlling the progression of colorectal cancer (CRC), making this disease a promising candidate for immunotherapy. However, responses to immune-targeted therapies are currently limited to subpopulations of patients and specific types of cancer. Clinical studies have therefore focussed on identifying biomarkers that predict immunotherapy responses and elucidating the immunological landscapes of different cancers. Meanwhile, our understanding of how preclinical tumour models resemble human disease has fallen behind, despite their crucial role in immune-targeted drug development. A deeper understanding of these models is therefore needed to improve the development of immunotherapies and the translation of findings made in these systems. MC38 colon adenocarcinoma is a widely used preclinical model, yet how it recapitulates human colorectal cancer remains poorly defined. This study investigated the tumour-T cell immune landscape of MC38 tumours using histology, immunohistochemistry, and flow cytometry. We demonstrate that early-stage tumours exhibit a nascent TME, lacking important immune-resistance mechanisms of clinical interest, while late-stage tumours exhibit a mature TME resembling human tumours, with desmoplasia, T cell exhaustion, and T cell exclusion. Consequently, these findings clarify appropriate timepoint selection in the MC38 model when investigating both immunotherapies and mechanisms that contribute to immunotherapy resistance. Overall, this study provides a valuable resource that will enable appropriate application of the MC38 model and expedite the development and clinical translation of new immunotherapies

Thermomechanical couplings in shape memory alloy materials

In this work we address several theoretical and computational issues which are related to the thermomechanical modeling of shape memory alloy materials. More specifically, in this paper we revisit a non-isothermal version of the theory of large deformation generalized plasticity which is suitable for describing the multiple and complex mechanisms occurring in these materials during phase transformations. We also discuss the computational implementation of a generalized plasticity based constitutive model and we demonstrate the ability of the theory in simulating the basic patterns of the experimentally observed behavior by a set of representative numerical examples

Mobility and the city improvement district: Frictions in the human-capital mobile assemblage

In this paper, we interrogate the role of the city improvement district (CID) in the intervention and management of mobility within the context of the South African city and the case study of the Groote Schuur Community Improvement District (GSCID), a public–private urban governance scheme situated in Cape Town’s middle income southern suburbs. Using the theoretical lens of bodily-scale mobility, we investigate the CID’s activation and management. This is useful, as we will demonstrate, because it is through the mobility and immobility at the scale of the body, where the CID’s mandate is operationalised and it is through the control of mobility that the CID’s mission, discourses and activities are linked. This work demonstrates that CIDs, as elite-driven urban renewal initiatives closely aligned with capital interests, employ exclusionary spatial practices that have the potential to shape the twenty-first century urban experience in significant ways. We conclude by theorising the co-constitutive nature of human mobilities and capital as the ‘human-capital mobile assemblage’ and by arguing that the CID occupies an ambivalent place in the contemporary city.IS

Effets comparés des inhibiteurs de l'enzyme de conversion et des antagonistes des récepteurs AT1 de l'angiotensine II sur l'insuffisance cardiaque

PARIS-BIUP (751062107) / SudocSudocFranceF