IL-1β turnover by the UBE2L3 ubiquitin conjugating enzyme and HECT E3 ligases limits inflammation

The cytokine interleukin-1β (IL-1β) has pivotal roles in antimicrobial immunity, but also incites inflammatory disease. Bioactive IL-1β is released following proteolytic maturation of the pro-IL-1β precursor by caspase-1. UBE2L3, a ubiquitin conjugating enzyme, promotes pro-IL-1β ubiquitylation and proteasomal disposal. However, actions of UBE2L3 in vivo and its ubiquitin ligase partners in this process are unknown. Here we report that deletion of Ube2l3 in mice reduces pro-IL-1β turnover in macrophages, leading to excessive mature IL-1β production, neutrophilic inflammation and disease following inflammasome activation. An unbiased RNAi screen identified TRIP12 and AREL1 E3 ligases of the Homologous to E6 C-terminus (HECT) family in adding destabilising K27-, K29- and K33- poly-ubiquitin chains on pro-IL-1β. We show that precursor abundance determines mature IL-1β production, and UBE2L3, TRIP12 and AREL1 limit inflammation by shrinking the cellular pool of pro-IL-1β. Our study uncovers fundamental processes governing IL-1β homeostasis and provides molecular insights that could be exploited to mitigate its adverse actions in disease

Method matters: Experimental evidence for shorter avian sperm in faecal compared to abdominal massage samples

Birds are model organisms in sperm biology. Previous work in zebra finches, suggested that sperm sampled from males faeces and ejaculates do not differ in size. Here, we tested this assumption in a captive population of house sparrows, Passer domesticus. We compared sperm length in samples from three collection techniques: female dummy, faecal and abdominal massage samples. We found that sperm were significantly shorter in faecal than abdominal massage samples, which was explained by shorter heads and midpieces, but not flagella. This result might indicate that faecal sampled sperm could be less mature than sperm collected by abdominal massage. The female dummy method resulted in an insufficient number of experimental ejaculates because most males ignored it. In light of these results, we recommend using abdominal massage as a preferred method for avian sperm sampling. Where avian sperm cannot be collected by abdominal massage alone, we advise controlling for sperm sampling protocol statistically.Funding Agencies|Volkswagen Foundation; International Max Planck Research School for Organismal Biology; [DFG:SCHR 1447/1-1]</p

The Impacts of Ict on leisure Activities and Travel: A Conceptual Exploration

This paper offers a conceptual exploration of the potential impacts of ICTs on leisure activities and the associated travel. We start by discussing what leisure is and is not. We point out that the boundaries between leisure, mandatory, and maintenance activities are permeable, for three reasons: the multi-attribute nature of a single activity, the sequential interleaving of activity fragments, and the simultaneous conduct of multiple activities (multitasking). We then discuss four kinds of ways by which ICT can affect leisure activities and travel: the replacement of a traditional activity with an ICT counterpart, the generation of new ICT activities (that may displace other activities), the ICT-enabled reallocation of time to other activities, and ICT as a facilitator of leisure activities. We suggest 13 dimensions of leisure activities that are especially relevant to the issue of ICT impacts: location (in)dependence, mobility-based versus stationary, time (in)dependence, planning horizon, temporal structure and fragmentation, possible multitasking, solitary versus social activity, active versus passive participation, physical versus mental, equipment/media (in)dependence, informal versus formal arrangements required, motivation, and cost. The primary impact of ICT on leisure is to expand an individual’s choice set; however whether or not the new options will be chosen depends on the attributes of the activity (such as the 13 identified dimensions), as well as those of the individual. The potential transportation impacts when the new options are chosen are ambiguous. Copyright Springer 2006information and communication technologies, leisure, telecommunication – travel,