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Bennion, A.

Publications and source records attributed to Bennion, A..

3 recordsLinked to original sources

Rhizobial motility preference in root colonization of Medicago truncatula

O_LITunnel-like infection thread (IT) structures support root colonization by symbiotic nitrogen-fixing rhizobia bacteria in most legume species. These tip-grown structures are key to direct rhizobia from root hairs to developing nodules, where they are hosted to fix nitrogen. Rhizobia likely progress inside ITs by combining growth and motility, by modes not yet defined. Here, we tackled this question by combining mathematical modeling, live cell imaging, and bacterial mutant phenotyping in Medicago truncatula. C_LIO_LIModeling the motion of fluorescently-labeled Sinorhizobium meliloti inside early root hair IT compartments estimated slow movement (2 to 6 {micro}m/h), compatible with passive rather than active motility. Consistent with this model, flagella-less fliF and fliF-fliRdel S. meliloti mutants were impaired in active swimming motility in vitro, yet could colonize host roots and nodules in planta. In contrast, mutation in the rhizobactin 1021 siderophore rhbE biosynthesis gene affected both surface motility in vitro, and host root and nodule colonisation. This mutation also promoted the formation of branched ITs in root hairs, which ultimately resulted in impaired nodule development and infection. C_LIO_LIOur findings support the model estimation and suggest that S. meliloti prioritises flagella-independent surface translocation, partially by secreting rhizobactin 1021 surfactants to reach developing nodules in M. truncatula. C_LI

plant biology↗

Multiscale Modeling Uncovers Macrophage Infiltration and TNF-α Signaling Networks for Targeting in Inflammatory Breast Cancer Tumor Emboli

Inflammatory breast cancer (IBC) tumors are characterized by diffuse clusters of cells found in dermal tissue and lymphatic vessels, known as tumor emboli. Thus, IBC needs a novel treatment because it is the most aggressive breast cancer subtype. We hypothesized that the interaction between tumor emboli and the tumor immune microenvironment (TiME) fosters survival signaling, leading to the aggressiveness of the IBC. In this study, ex vivo tumor emboli were generated from patient-derived cell lines cultured in a lymphatic-like environment, which was compared to 2D monolayer cultures, revealing upregulation of TNFR signaling networks, CXCL8, and immune cell chemotaxis genes. Spatial immunophenotyping of IBC patient tumors demonstrated high levels of CD163+ tumor-associated macrophages (TAMs). Furthermore, intravital imaging of CX3cr1GFP mice confirmed macrophage movement toward tumor cell clusters. Finally, targeting macrophage-associated TNF--signaling using Birinapant, a SMAC mimetic, inhibited the tumor emboli phenotype in vivo, identifying Birinapant as a potential therapeutic agent to disrupt this signaling axis.

cancer biology↗

Dissociating the effect of reward uncertainty and timing uncertainty on neural indices of reward prediction errors: A reward positivity (RewP) event-related potential (ERP) study

Accurate reward predictions include forecasting both what a reward will be and when a reward will occur. We tested how variations in the certainty of reward outcome and certainty in timing of feedback presentation modulate neural indices of reward prediction errors using the reward positivity (RewP) component of the scalp-recorded brain event-related potential (ERP). In a within-subjects design, seventy-three healthy individuals completed two versions of a cued doors task; one cued the probability of a reward outcome while the other cued the probability of a delay before feedback. Replicating previous results, RewP amplitude was larger for uncertain feedback compared to certain feedback. Additionally, RewP amplitude was differentially associated with uncertainty of presence/absence of reward, but not uncertainty of feedback timing. Findings suggest a dissociation in that RewP amplitude is modulated by reward prediction certainty but is less affected by certainty surrounding timing of feedback.

neuroscience↗