IL-1 beta-converting enzyme (ICE) cleaves pro-IL-1 beta to generate mature IL-1 beta. ICE is homologous to other proteins that have been implicated in apoptosis, including CED-3 and Nedd-2/lch-1. We generated ICE-deficient mice and observed that they are overtly normal but have a major defect in the production of mature IL-1 beta after stimulation with lipopolysaccharide. IL-1 alpha production is also impaired. ICE-deficient mice are resistant to endotoxic shock. Thymocytes and macrophages from the ICE-deficient animals undergo apoptosis normally. ICE therefore plays a dominant role in the generation of mature IL-1 beta, a previously unsuspected role in production of IL-1 alpha, but has no autonomous function in apoptosis.

The baculovirus antiapoptotic protein p35 inhibited the proteolytic activity of human interleukin-1 beta converting enzyme (ICE) and three of its homologs in enzymatic assays. Coexpression of p35 prevented the autoproteolytic activation of ICE from its precursor form and blocked ICE-induced apoptosis. Inhibition of enzymatic activity correlated with the cleavage of p35 and the formation of a stable ICE-p35 complex. The ability of p35 to block apoptosis in different pathways and in distantly related organisms suggests a central and conserved role for ICE-like proteases in the induction of apoptosis.

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Habitual footwear use has been reported to influence foot structure with an acute exposure being shown to alter foot position and mechanics. The foot is highly specialised thus these changes in structure/position could influence functionality. This review aims to investigate the effect of footwear on gait, specifically focussing on studies that have assessed kinematics, kinetics and muscle activity between walking barefoot and in common footwear. In line with PRISMA and published guidelines, a literature search was completed across six databases comprising Medline, EMBASE, Scopus, AMED, Cochrane Library and Web of Science. Fifteen of 466 articles met the predetermined inclusion criteria and were included in the review. All articles were assessed for methodological quality using a modified assessment tool based on the STROBE statement for reporting observational studies and the CASP appraisal tool. Walking barefoot enables increased forefoot spreading under load and habitual barefoot walkers have anatomically wider feet. Spatial-temporal differences including, reduced step/stride length and increased cadence, are observed when barefoot. Flatter foot placement, increased knee flexion and a reduced peak vertical ground reaction force at initial contact are also reported. Habitual barefoot walkers exhibit lower peak plantar pressures and pressure impulses, whereas peak plantar pressures are increased in the habitually shod wearer walking barefoot. Footwear particularly affects the kinematics and kinetics of gait acutely and chronically. Little research has been completed in older age populations (50+ years) and thus further research is required to better understand the effect of footwear on walking across the lifespan.

We show that helping young job-seekers signal their skills to employers generates large and persistent improvements in their labour market outcomes. We do this by comparing an intervention that improves the ability to signal skills (the ‘job application workshop’) to a transport subsidy treatment designed to reduce the cost of job search. In the short-run, both interventions have large positive effects on the probability of finding a formal job. The workshop also increases the probability of having a stable job with an open-ended contract. Four years later, the workshop significantly increases earnings, job satisfaction, and employment duration, but the effects of the transport subsidy have dissipated. Gains are concentrated on individuals who generally have worse labour market outcomes. Overall, our findings highlight that young people possess valuable skills that are unobservable to employers. Making these skills observable generates earnings gains that are far greater than the cost of the intervention.