UbC is one of two stress‐inducible polyubiquitin genes in mammals and is thought to supplement the constitutive UbA genes in maintaining cellular ubiquitin (Ub) levels during episodes of cellular stress. We have generated mice harboring a targeted disruption of the UbC gene. UbC−/− embryos die between embryonic days 12.5 and 14.5 in utero, most likely owing to a severe defect in liver cell proliferation. Mouse embryonic fibroblasts from UbC−/− embryos exhibit reduced growth rates, premature senescence, increased apoptosis and delayed cell‐cycle progression, with slightly, but significantly, decreased steady‐state Ub levels. UbC−/− fibroblasts are hypersensitive to proteasome inhibitors and heat shock, and unable to adequately increase Ub levels in response to these cellular stresses. Most, but not all of the UbC−/− phenotypes can be rescued by providing additional Ub from a poly hemagglutinin‐tagged Ub minigene expressed from the Hprt locus. We propose that UbC is regulated by a process that senses Ub pool dynamics. These data establish that UbC constitutes an essential source of Ub during cell proliferation and stress that cannot be compensated by other Ub genes.

Vitamin D supplementation during pregnancy and infancy reduces the proportion of children sensitized to mites at age 18 months. Preliminary data indicate a possible effect on primary care visits where asthma is diagnosed.

Ubiquitin is a small eukaryotic protein that is synthesized naturally as one of several fusion proteins, which are processed by ubiquitin-specific proteases to release free ubiquitin. The expression of heterologous proteins as fusions to ubiquitin in either prokaryotic or eukaryotic hosts often dramatically enhances their yield, and allows the exposure of any amino acid following cleavage of ubiquitin. The single exception is when proline is the amino acid immediately following ubiquitin; the ubiquitin-proline bond is poorly cleaved by presently studied ubiquitin-specific proteases. We show that the mouse ubiquitin-specific protease Unp, and its human homolog Unph, can efficiently cleave the ubiquitin-proline bond in ubiquitin fusion proteins of different sizes. N-terminal sequencing of the cleavage products reveals that cleavage occurs precisely at the ubiquitin-proline junction. The biological significance of this cleavage activity is unclear, as ubiquitin-proline fusions do not occur naturally. However, it may indicate a different catalytic mechanism for these ubiquitin-specific proteases and/or that they can cleave ubiquitin-like proteins. Unp and Unph thus represent versatile ubiquitin-specific proteases for cleaving ubiquitin-fusion proteins in biotechnology and basic research, regardless of both the amino acid immediately following ubiquitin, and the size of the fusion partner.

Background:In children, community-acquired pneumonia is a frequent cause of emergency department (ED) presentation and hospital admission. Quality primary care may prevent some of these hospital visits.Aims:The aim of this study was to identify primary care factors associated with ED presentation and hospital admission of preschool-aged children with community-acquired pneumonia.Methods:A case–control study was conducted by enrolling three groups: children presenting to the ED with pneumonia and admitted (n=326), or discharged home (n=179), and well-neighbourhood controls (n=351). Interviews with parents and primary care staff were conducted and health record review was performed. The association of primary care factors with ED presentation and hospital admission, controlling for available confounding factors, was determined using logistic regression.Results:Children were more likely to present to the ED with pneumonia if they did not have a usual general practitioner (GP) (odds ratio (OR)=2.50, 95% confidence interval (CI)=1.67–3.70), their GP worked ⩽20 h/week (OR=1.86, 95% CI=1.10–3.13) or their GP practice lacked an immunisation recall system (OR=5.44, 95% CI=2.26–13.09). Lower parent ratings for continuity (OR=1.63, 95% CI=1.01–2.62), communication (OR=2.01, 95% CI=1.29–3.14) and overall satisfaction (OR=2.16, 95% CI=1.34–3.47) increased the likelihood of ED presentation. Children were more likely to be admitted when antibiotics were prescribed in primary care (OR=2.50, 95% CI=1.43–4.55). Hospital admission was less likely if children did not have a usual GP (OR=0.22, 95% CI=0.11–0.40) or self-referred to the ED (OR=0.48, 95% CI=0.26–0.89).Conclusions:Accessible and continuous primary care is associated with a decreased likelihood of preschool-aged children with pneumonia presenting to the ED and an increased likelihood of hospital admission, implying more appropriate referral. Lower parental satisfaction is associated with an increased likelihood of ED presentation.