Ureaplasma parvum undergoes selection in utero resulting in genetically diverse isolates colonising the chorioamnion of fetal sheep

Ureaplasmas are the microorganisms most frequently isolated from the amniotic fluid of pregnant women and can cause chronic intrauterine infections. These tiny bacteria are thought to undergo rapid evolution and exhibit a hypermutatable phenotype; however, little is known about how ureaplasmas respond to selective pressures in utero. Using an ovine model of chronic intra-amniotic infection, we investigated if exposure of ureaplasmas to sub-inhibitory concentrations of erythromycin could induce phenotypic or genetic indicators of macrolide resistance. At 55 days gestation, 12 pregnant ewes received an intra-amniotic injection of a non-clonal, clinical U. parvum strain, followed by: (i) erythromycin treatment (IM, 30 mg/kg/day, n=6); or (ii) saline (IM, n=6) at 100 days gestation. Fetuses were then delivered surgically at 125 days gestation. Despite injecting the same inoculum into all ewes, significant differences between amniotic fluid and chorioamnion ureaplasmas were detected following chronic intra-amniotic infection. Numerous polymorphisms were observed in domain V of the 23S rRNA gene of ureaplasmas isolated from the chorioamnion (but not the amniotic fluid), resulting in a mosaic-like sequence. Chorioamnion isolates also harboured the macrolide resistance genes erm(B) and msr(D) and were associated with variable roxithromycin minimum inhibitory concentrations. Remarkably, this variability occurred independently of exposure of ureaplasmas to erythromycin, suggesting that low-level erythromycin exposure does not induce ureaplasmal macrolide resistance in utero. Rather, the significant differences observed between amniotic fluid and chorioamnion ureaplasmas suggest that different anatomical sites may select for ureaplasma sub-types within non-clonal, clinical strains. This may have implications for the treatment of intrauterine ureaplasma infections.

Contemporary comments: The limited benefit of prison in controlling crime

A number of recent developments in the United State (US), United Kingdom (UK) and Australia suggest that conditions may be ripe for a political shift in the reliance on escalating rates of imprisonment as a default criminal justice strategy for responding to crime. The default position is illustrated by the Yabsleyite response of former New South Wales (NSW) Premier Nathan Rees���s to questioning over the cost of prison building and NSW���s high recidivism rate: ���[t]he advice to me is we have still got 500 cells empty, I don't mind if we fill them up, and if we fill them up and have to build another jail, we'll build another jail��� (Knox and Tadros 2008)...

���A contributing life���: Living a contributing life as ���a person���, ���an artist��� and ���an artist with a mental illness���

The Australian National Mental Health Commission, recently adopted a focus on ���a contributing life��� to acknowledge the importance of full and meaningful participation in community life. This concept compels new conversations about the complex nature of every day and whole of life experiences for people with lived experience of mental illness. This article reflects on narratives by eight artists with lived experience of mental illness, in Australia to understand how opportunities are available through art for people with lived experience of mental illness to lead a contributing life. A twelve month study gained insight of how participants saw themselves, made meaning and sense of their experiences, and how each person asserted their choice to be an artist. This article shares a common premise held by the participants to choose a ���way of life as ���who I am������. This declaration emphasised the relevance of living a contributing life as ���a person���, ���an artist��� and ���an artist with a mental illness���. A number of conceptual issues are raised in light of the findings, not least how opportunities for participation are framed and available, or otherwise, to live a contributing life.

A grounded theory of living a life with a physical disability in Taiwan

This study explores the experiences of disability for a number of Taiwanese adults with a physical disability. Using a grounded theory approach, their experiences of living a life with a physical disability were gained through in-depth interviews. The resulting grounded theory ���it is more than just the impaired body��� presents the dynamic interactions between the participants and the context in which they were living their lives and how they managed their lives within that context. With its inclusion of the cultural dimension, a holistic way of understanding the daily lives of those who experience physical disability in Taiwan is provided.

Breastmilk-saliva interactions boost innate immunity by regulating the oral microbiome in early infancy

Introduction Xanthine oxidase (XO) is distributed in mammals largely in the liver and small intestine, but also is highly active in milk where it generates hydrogen peroxide (H2O2). Adult human saliva is low in hypoxanthine and xanthine, the substrates of XO, and high in the lactoperoxidase substrate thiocyanate, but saliva of neonates has not been examined. Results Median concentrations of hypoxanthine and xanthine in neonatal saliva (27 and 19 ��M respectively) were ten-fold higher than in adult saliva (2.1 and 1.7 ��M). Fresh breastmilk contained 27.3��12.2 ��M H2O2 but mixing baby saliva with breastmilk additionally generated >40 ��M H2O2, sufficient to inhibit growth of the opportunistic pathogens Staphylococcus aureus and Salmonella spp. Oral peroxidase activity in neonatal saliva was variable but low (median 7 U/L, range 2���449) compared to adults (620 U/L, 48���1348), while peroxidase substrate thiocyanate in neonatal saliva was surprisingly high. Baby but not adult saliva also contained nucleosides and nucleobases that encouraged growth of the commensal bacteria Lactobacillus, but inhibited opportunistic pathogens; these nucleosides/bases may also promote growth of immature gut cells. Transition from neonatal to adult saliva pattern occurred during the weaning period. A survey of saliva from domesticated mammals revealed wide variation in nucleoside/base patterns. Discussion and Conclusion During breast-feeding, baby saliva reacts with breastmilk to produce reactive oxygen species, while simultaneously providing growth-promoting nucleotide precursors. Milk thus plays more than a simply nutritional role in mammals, interacting with infant saliva to produce a potent combination of stimulatory and inhibitory metabolites that regulate early oral���and hence gut���microbiota. Consequently, milk-saliva mixing appears to represent unique biochemical synergism which boosts early innate immunity.

Placental infection with Ureaplasma species is associated with histologic chorioamnionitis and adverse outcomes in moderately preterm and late-preterm infants

Objective The human Ureaplasma species are the microbes most frequently isolated from placentae of women who deliver preterm. The role of Ureaplasma species has been investigated in pregnancies at <32 weeks of gestation, but currently no studies have determined the prevalence of ureaplasmas in moderately preterm and late-preterm (hereafter, ���moderate/late preterm���) infants, the largest cohort of preterm infants. Methods Women delivering moderate/late preterm infants (n = 477) and their infants/placentae (n = 535) were recruited, and swab specimens of chorioamnion tissue, chorioamnion tissue specimens, and cord blood specimens were obtained at delivery. Swab and tissue specimens were cultured and analyzed by 16S ribosomal RNA polymerase chain reaction (PCR) for the presence of microorganisms, while cord blood specimens were analyzed for the presence of cytokines, chemokines, and growth factors. Results We detected microorganisms in 10.6% of 535 placentae (443 were delivered late preterm and 92 were delivered at term). Significantly, Ureaplasma species were the most prevalent microorganisms, and their presence alone was associated with histologically confirmed chorioamnionitis in moderate/late preterm and term placentae (P < .001). The presence of ureaplasmas in the chorioamnion was also associated with elevated levels of granulocyte colony-stimulating factor (P = .02). Conclusions These findings have important implications for infection and adverse pregnancy outcomes throughout gestation and should be of major consideration for obstetricians and neonatologists.

A promoter-level mammalian expression atlas

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.