Lupine and zig-zag lines: queer affects in Alain Guiraudie’s L’inconnu du lac and Rester vertical

In this article I investigate how a theory of becomings-animal operates in a number of contemporary queer French films by director Alain Guiraudie (L’inconnu du lac (2013) and Rester vertical (2016)). In particular I explore how a becomings-animal’s association with a Deleuzian theory of affect enhances our understanding of queer intimacy. The aim of this article is to reposition queer intimacy as an ontology outside – outside synthetic and vertical lines of filiation and kinship and inside the disjunctive lines of the outside (what is irregular, random, rural, cosmic). Drawing at first on intimacy as an ontological non-relationality (Bersani 2008; 2009) and on the idea of separation as an ontological necessity of queer intimacy (John Paul Ricco 2017), I want to rethink queer intimacy as exposure outwards – an intimacy to and towards. Within this exteriorization of intimacy, my methodology will rely on the affective power of a Deleuzian theory of lines

Breast erythema and nodular skin metastasis as the first manifestation of breast implant-associated anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (BIA-ALCL) associated with rough textured breast implants was first reported in 1997. It is a non-Hodgkin's lymphoma originating from a T lymphocyte which occurs on average 10.9 years after placement of the breast implant. BIA-ALCL mainly manifests as a periprosthetic seroma or a mass adjacent to the implant. To our knowledge, we describe the first case of BIA-ALCL with initial presentation by indurate erythematous plates located in both breasts and the progressive appearance of several asymptomatic metastatic nodular lesions that have been appearing on the right arm some weeks later

The nuclear receptor FXR inhibits Glucagon-Like Peptide-1 secretion in response to microbiota-derived Short-Chain Fatty Acids.

The gut microbiota participates in the control of energy homeostasis partly through fermentation of dietary fibers hence producing short-chain fatty acids (SCFAs), which in turn promote the secretion of the incretin Glucagon-Like Peptide-1 (GLP-1) by binding to the SCFA receptors FFAR2 and FFAR3 on enteroendocrine L-cells. We have previously shown that activation of the nuclear Farnesoid X Receptor (FXR) decreases the L-cell response to glucose. Here, we investigated whether FXR also regulates the SCFA-induced GLP-1 secretion. GLP-1 secretion in response to SCFAs was evaluated ex vivo in murine colonic biopsies and in colonoids of wild-type (WT) and FXR knock-out (KO) mice, in vitro in GLUTag and NCI-H716 L-cells activated with the synthetic FXR agonist GW4064 and in vivo in WT and FXR KO mice after prebiotic supplementation. SCFA-induced GLP-1 secretion was blunted in colonic biopsies from GW4064-treated mice and enhanced in FXR KO colonoids. In vitro FXR activation inhibited GLP-1 secretion in response to SCFAs and FFAR2 synthetic ligands, mainly by decreasing FFAR2 expression and downstream Gαq-signaling. FXR KO mice displayed elevated colonic FFAR2 mRNA levels and increased plasma GLP-1 levels upon local supply of SCFAs with prebiotic supplementation. Our results demonstrate that FXR activation decreases L-cell GLP-1 secretion in response to inulin-derived SCFA by reducing FFAR2 expression and signaling. Inactivation of intestinal FXR using bile acid sequestrants or synthetic antagonists in combination with prebiotic supplementation may be a promising therapeutic approach to boost the incretin axis in type 2 diabetes

Ffar2 expression regulates leukaemic cell growth in vivo.

BACKGROUND: Activation of free fatty acid receptor 2 (FFAR2) by microbiota-derived metabolites (e.g., propionate) reduces leukaemic cell proliferation in vitro. This study aims to test whether Ffar2 expression per se also influences leukaemia cell growth in vivo. METHODS: Bcr-Abl-expressing BaF cells were used as a leukaemia model and the role of Ffar2 was evaluated in Balb/c mice after lentiviral shRNA transduction. RESULTS: Our data formally establish that reduced leukaemic cell proliferation is associated with increased Ffar2 expression in vivo and in vitro. Going beyond association, we point out that decreasing Ffar2 expression fosters cancer cell growth in vitro and in vivo. CONCLUSIONS: Our data demonstrate the role of Ffar2 in the control of leukaemic cell proliferation in vivo and indicate that a modulation of Ffar2 expression through nutritional tools or pharmacological agents may constitute an attractive therapeutic approach to tackle leukaemia progression in humans

Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells.

Bile acids are signalling molecules, which activate the transmembrane receptor TGR5 and the nuclear receptor FXR. BA sequestrants (BAS) complex bile acids in the intestinal lumen and decrease intestinal FXR activity. The BAS-BA complex also induces glucagon-like peptide-1 (GLP-1) production by L cells which potentiates β-cell glucose-induced insulin secretion. Whether FXR is expressed in L cells and controls GLP-1 production is unknown. Here, we show that FXR activation in L cells decreases proglucagon expression by interfering with the glucose-responsive factor Carbohydrate-Responsive Element Binding Protein (ChREBP) and GLP-1 secretion by inhibiting glycolysis. In vivo, FXR deficiency increases GLP-1 gene expression and secretion in response to glucose hence improving glucose metabolism. Moreover, treatment of ob/ob mice with the BAS colesevelam increases intestinal proglucagon gene expression and improves glycaemia in a FXR-dependent manner. These findings identify the FXR/GLP-1 pathway as a new mechanism of BA control of glucose metabolism and a pharmacological target for type 2 diabetes