Selective stimulation of IL-4 receptor on smooth muscle induces airway hyperresponsiveness in mice

IL-4Rα expression on airway smooth muscle cells is sufficient for the development of airway hyperresponsiveness

Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy

Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with a severe, progressive muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD) but of much earlier onset, caused by heterozygous frameshift variants in the RBP hnRNPA2/B1. All disease-causing frameshift mutations abolish the native stop codon and extend the reading frame, creating novel transcripts that escape nonsense-mediated decay and are translated to produce hnRNPA2/B1 protein with the same neomorphic C-terminal sequence. In contrast to previously reported disease-causing missense variants in HNRNPA2B1, these frameshift variants do not increase the propensity of hnRNPA2 protein to fibrillize. Rather, the frameshift variants have reduced affinity for the nuclear import receptor karyopherin β2, resulting in cytoplasmic accumulation of hnRNPA2 protein in cells and in animal models that recapitulate the human pathology. Thus, we expand the phenotypes associated with HNRNPA2B1 to include an early-onset form of OPMD caused by frameshift variants that alter its nucleocytoplasmic transport dynamics

Toilets, bodies, selves: enacting composting as counterculture in Hawai'i

Defecation has received limited attention within the social sciences and humanities. Toilets not a great deal. Urination even less. However, examining the practice of composting faeces and ‘pee[ing] on any tree’ by white, West Coast US ‘hippies’ and ‘drop-outs’ living in Hawai’i suggests that the disposal of excreta is never simple disposal. Rather, it entails engagement with the state, one’s own body and sense of placedness. Through looking at the everyday defecatory practices of hippies and drop-outs in Hawai’i, this article seeks to examine the interplay of the act of defecation and urination with the materiality of toilets themselves. Each depends on the other, and both exist in relation to various others: other toilet designs, other communities, other people. As such, it becomes possible to extend beyond Douglas’s argument that ‘dirt is matter out of place’ to explore the notion that – at least in relation to toilets – ‘dirt is relations out of place’. By placing relationships at the heart of this analysis of defecation and urination, this article provides fertile ground for the exploration of embodiment at its most base level, as site of generative action and social critique