Liver, visceral and subcutaneous fat in men and women of South Asian and white European descent: a systematic review and meta-analysis of new and published data

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Non-canonical Caspase-1 signaling drives RIP2-dependent and TNF-α-mediated inflammation in vivo

Pro-inflammatory caspase-1 is a key player in innate immunity. Caspase-1 processes interleukin (IL)-1β and IL-18 to their mature forms and triggers pyroptosis. These caspase-1 functions are linked to its enzymatic activity. However, loss-of-function missense mutations in CASP1 do not prevent autoinflammation in patients, despite decreased IL-1β production. In vitro data suggest that enzymatically inactive caspase-1 drives inflammation via enhanced nuclear factor κB (NF-κB) activation, independent of IL-1β processing. Here, we report two mouse models of enzymatically inactive caspase-1-C284A, demonstrating the relevance of this pathway in vivo. In contrast to Casp1 mice, caspase-1-C284A mice show pronounced hypothermia and increased levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and IL-6 when challenged with lipopolysaccharide (LPS). Caspase-1-C284A signaling is RIP2 dependent and mediated by TNF-α but independent of the NLRP3 inflammasome. LPS-stimulated whole blood from patients carrying loss-of-function missense mutations in CASP1 secretes higher amounts of TNF-α. Taken together, these results reveal non-canonical caspase-1 signaling in vivo.Reinke et al. show that enzymatically inactive caspase-1-C284A mediates non-canonical caspase-1 signaling. This pathway is RIP2 dependent and mediated by TNF-α but independent from IL-1 cytokines

Odour perception: A review of an intricate signalling pathway

The perception of odours is the result of the complex processing of a signal, which initiates at peripheral receptors and ends in the brain. Along this pathway, olfactory signal processing proceeds through several steps; each step possesses its own complexity, and all steps are also intricately connected. This review aims to describe the main intricate steps of olfactory processing in mammals, some of which remain unclear, and the close associations and overlapping nature of these steps. The causes of both the complexity and the variability of olfactory signals are examined: the nature of olfactory receptors, involving the diversity of the genome; the spatial organization of the olfactory epithelium (OE) and the olfactory bulb (OB); connections in the OB and from the OB to the brain; integration and processing in the brain, which leads to the final perception of odours; and odour recognition and odour identification, which is associated with the difficulty to verbalize a reliable description of the perception in humans. Finally, the last part of this review encompasses recent progress made to decipher and understand olfactory coding and focuses on computational approaches