Flightless, secreted through a late endosome/lysosome pathway, binds LPS and dampens cytokine secretion.

Flightless (Flii) is upregulated in response to wounding and has been shown to function in wound closure and scarring. In macrophages intracellular Flii negatively modulates TLR signalling and dampens cytokine production. We now show that Flii is constitutively secreted from macrophages and fibroblasts and is present in human plasma. Secretion from fibroblasts is upregulated in response to scratch wounding and LPS-activated macrophages also temporally upregulate their secretion of Flii. Using siRNA, wild-type and mutant proteins we show that Flii is secreted via a late endosomal/lysosomal pathway that is regulated by Rab7 and Stx11. Flii contains 11 leucine rich repeat (LRR) domains in its N-terminus that have nearly 50% similarity to those in the extracellular pathogen binding portion of Toll-like receptor 4 (TLR4). We show secreted Flii can also bind LPS and has the ability to alter macrophage activation. LPS activation of macrophages in Flii depleted conditioned media leads to enhanced macrophage activation and increased TNF secretion compared to cells activated in the presence of Flii. These results show secreted Flii binds to LPS and in doing so alters macrophage activation and cytokine secretion, suggesting that like the intracellular pool of Flii, secreted Flii also has the ability to alter inflammation.

Identity and genetic origins : an ethical exploration of the late discovery of adoptive and donor-insemination offspring status

This thesis is an ethical and empirical exploration of the late discovery of genetic origins in two contexts, adoption and sperm donor-assisted conception. This exploration has two interlinked strands of concern. The first is the identification of ‘late discovery’ as a significant issue of concern, deserving of recognition and acknowledgment. The second concerns the ethical implications of late discovery experiences for the welfare of the child. The apparently simple act of recognition of a phenomenon is a precondition to any analysis and critique of it. This is especially important when the phenomenon arises out of social practices that arouse significant debate in ethical and legal contexts. As the new reproductive technologies and some adoption practices remain highly contested, an ethical exploration of this long neglected experience has the potential to offer new insights and perspectives in a range of contexts. It provides an opportunity to revisit developmental debate on the relative merit or otherwise of biological versus social influences, from the perspective of those who have lived this dichotomy in practise. Their experiences are the human face of the effects arising from decisions taken by others to intentionally separate their biological and social worlds, an action which has then been compounded by family and institutional secrecy from birth. This has been accompanied by a failure to ensure that normative standards and values are upheld for them. Following discovery, these factors can be exacerbated by a lack of recognition and acknowledgement of their concerns by family, friends, community and institutions. Late discovery experiences offer valuable insights to inform discussions on the ethical meanings of child welfare, best interests, parental responsibility, duty of care and child identity rights in this and other contexts. They can strengthen understandings of what factors are necessary for a child to be able to live a reasonably happy or worthwhile life.

Explaining Gendered Sentencing Patterns for Men and Women in the Late Victorian Period

Contemporary studies of disparities in the sentencing of male and female offenders claim that the differences found are caused by gender-related contextual factors, but not by a gender bias. In contrast, historical studies have suggested that women were disadvantaged by appearing to offend both against the law and the conventions of femininity. This article analyses minor assaults prosecuted in ten English magistrates’ courts between 1880 and 1920. It is based on a data-set that combines court cases and newspaper reports, and allows for the control of gender differences in sentencing outcomes through four contextual factors: severity of the assault, bonds between victim and assailant, culpability, and evidence. The findings reveal a differentiated pattern of sentences that questions the assumption that ‘doubly deviant’ women were more often convicted, and received higher penalties, throughout the Victorian period. The results show that the contextual factors of the offence affected judicial decision-making to the extent that they virtually account for gender differences in conviction rates, but do not, on their own, account for the different penalties handed out to men and women. Women who committed similar assaults to men were likely to receive a lighter punishment. Magistrates clearly targeted ‘male’ contexts of violence, and handed down more convictions and harsher penalties to men involved in these, in contrast to women involved in 'female' contexts. The findings of a strong gender bias in sentencing that disadvantaged lowerclass men indicate that local magistrates directed their efforts of 'civilizing' lower-class communities at 'dangerous masculinities', and deemed assaults committed by women as less important in this task.

The late discovery of adoptive and donor insemination offspring status : ethical implications for conceptual understandings of the ‘best interests of the child’ principle

Late discovery is a term used to describe the experience of discovering the truth of one’s genetic origins as an adult. Following discovery, late discoverers face a lack of recognition and acknowledgment of their concerns from family, friends, community and institutions. They experience pain, anger, loss, grief and frustration. This presentation shares the findings of the first qualitative study of both late discovery of adoptive and donor insemination offspring (heterosexual couple use only) experiences. It is also the first study of late discovery experiences undertaken from an ethical perspective. While this study recruited new participants, it also included an ethical re-analysis of existing late discovery accounts across both practices. The findings of this study (a) draws links between past adoption and current donor insemination (heterosexual couple only) practices, (b) reveals that late discoverers are demanding acknowledgment and recognition of the particularity of their experiences, and (c) offers insights into conceptual understandings of the ‘best interests of the child’ principle. These insights derive from the lived experiences of those whose biological and social worlds have been sundered and secrecy and denial of difference used to conceal this. It suggests that acknowledging the equal moral status of the child may be useful in strengthening conceptual understandings of the ‘best interests of the child’ principle. This equal moral status involves ensuring that personal autonomy and the ability to exercise free will is protected; that the integrity of the relationships of trust expected and demanded between parent/s and children is defended and supported; and that equal access to normative socio-cultural practices, that is; non-fictionalised birth certificates and open records, is guaranteed.

Ureaplasma speioces are associated with chorioamnionitiis in late preterm placentas

Background: Preterm birth is a major cause of neonatal morbidity and mortality, with 75% of preterm births occurring late preterm. Previous studies have investigated the microbial diversity within placentas delivered early preterm but there has been no investigation of the prevalence of bacteria, particularly Ureaplasma spp. in late preterm placentas. Method: Women giving birth late preterm (320 – 366 weeks of gestation) in Cincinnati were recruited for this study. Samples of chorioamnion were collected aseptically at the time of delivery, shipped to QUT and tested for Ureaplasma spp. and other bacteria by culture and/or PCR assays. The presence of bacteria was correlated with adverse pregnancy outcomes, including histological chorioamnionitis (tissue sections read by US pathologists). Results: To date, Ureaplasma spp. have been detected in 15/270 (5.5%) of placentas by culture and 19/270 (7%) by PCR. Ureaplasma presence correlated with histological chorioamnionitis (12/19%; 63%). However, the presence of other bacteria was not associated with chorioamnionitis (5%). Chorioamnionitis was unevenly distributed in ethnic groups, with a higher incidence in African-Americans’ (6/7; 86%), compared to Caucasians’ (6/12; 50%) who were colonised with ureaplasmas. Conclusion: This study is the first to report the prevalence of ureaplasmas in women (7%) who deliver late preterm. Ureaplasma spp. were associated with a higher incidence of chorioamnionitis (63% compared to 15% for non-infected women). This data strongly suggests that ureaplasmas are a cause of late preterm deliveries and African-American women are at greater risk of chorioamnionitis.

Characterisation of micrinite in the late triassic Callide Coal Measures

Samples from the Callide Coal Measures, Queensland, Australia, containing the minor maceral, micrinite, have been studied using optical and electron-optical techniques to determine the precise compositional and structural nature of micrinite when in association with vitrinite macerals. Emphasis has been placed on direct spatial correlation of optical and electron-optical data due to the fine grain size (<1μm) of micrinite and its relatively low abundance compared with other macerals in the Callide Basin coals. Precise elemental, morphological and structural data, including electron diffraction, provides unambiguous evidence for the presence of kaolinite in the component known as micrinite. Indeed, micrinite consists predominantly of fine-grained kaolinite (>90 per cent of the component) and, as such, should not be considered a maceral.

Pulling apart the mid to late Cenozoic magmatic record of the Gulf of California : no room for the Comondú Arc

Understanding the link between tectonic-driven extensional faulting and volcanism is crucial from a hazard perspective in active volcanic environments, while ancient volcanic successions provide records on how volcanic eruption styles, compositions, magnitudes and frequencies can change in response to extension timing, distribution and intensity. Significantly, incorrect tectonic interpretations can be made when the spatial-temporal-compositional trends of, and source contributions to magmatism are not properly considered. This study draws on intimate relationships of volcanism and extension preserved in the Sierra Madre Occidental (SMO) and Gulf of California (GoC) regions of western Mexico. Here, a major Oligocene rhyolitic ignimbrite “flare-up” (>300,000 km3) switched to a dominantly bimodal and mixed effusive-explosive volcanic phase in the Early Miocene (~100,000 km3), associated with distributed extension and opening of numerous grabens. Rhyolitic dome fields were emplaced along graben edges and at intersections of cross-graben and graben-parallel structures during early stages of graben development. Concomitant with this change in rhyolite eruption style was a change in crustal source as revealed by zircon chronochemistry with rapid rates of rhyolite magma generation due to remelting of mid- to upper crustal, highly differentiated igneous rocks emplaced during earlier SMO magmatism. Extension became more focused ~18 Ma resulting in volcanic activity being localised along the site of GoC opening. This localised volcanism (known as the Comondú “arc”) was dominantly effusive and andesite-dacite in composition. This compositional change resulted from increased mixing of basaltic and rhyolitic magmas rather than fluid flux melting of the mantle wedge above the subducting Guadalupe Plate. A poor understanding of space-time relationships of volcanism and extension has thus led to incorrect past tectonic interpretations of Comondú-age volcanism.

Late Oligocene to middle Miocene rifting and syn-extensional magmatism in the southwestern Sierra Madre occidental, Mexico: the beginning of the Gulf of California rift

Although Basin and Range style extension affected several areas of western Mexico since the Late Eocene, extension in the Gulf of California region (the Gulf Extensional Province GEP) is thought to have started as subduction waned and ended at ~14 12.5 Ma. A general consensus also exists in considering the mid Miocene Comondú group as a suprasubduction volcanic arc. Our new integration of the geology of the south east Gulf region, backed by 43 new Ar Ar and U Pb mineral ages and geochemical studies, document a widespread phase of extension in the southern GEP between latest Oligocene and Early Miocene that subsequently focused in the region of the future Gulf in the Middle Miocene. Upper Oligocene to Lower Miocene rocks across the southern Sierra Madre Occidental (SMO)(northern Nayarit and southern Sinaloa) were affected by major ~N S to NNW striking normal faults prior to ~21 Ma. Then, between ~21 and 11 Ma, a system of NNW-SSE high angle extensional faults continued extending the southwestern side of the SMO. Rhyolitic domes, shallow intrusive bodies, and lesser basalts were emplaced along this extensional belt at 20-17 Ma. In northern Sinaloa, large grabens were floored by huge dome complexes at ~21-17 Ma and filled by continental sediments with interlayered basalts dated at 15-14 Ma, a setting and timing very similar to Sonora. Early to Middle Miocene volcanism, including the largely volcaniclastic Comondú strata in Baja California Sur, was thus emplaced in rift basins and was likely associated to decompression melting of upper mantle (inducing crustal partial melting) rather than to fluxing by fluids from the young subducting plate. Along the Nayarit and Sinaloa coast, flatlying basaltic lava flows dated at 11-10 Ma are exposed just above the present sea level. Here, crustal thickness is almost half that in the unextended core of the SMO, implying significant lithosphere stretching before ~11 Ma. Our study shows that rifting began much earlier than Late Miocene and provided a fundamental control on the style and composition of volcanism from at least 30 Ma. We envision a sustained period of lithospheric stretching and magmatism during which the pace and breadth of extension changed at ~20-18 Ma to be narrower and likely more rapid, and again at ~12.5 Ma, when the kinematics of rifting became more oblique.

Early-mid Cretaceous tectonic evolution of eastern Gondwana : from silicic LIP magmatism to continental rupture

The Early–mid Cretaceous marks the confluence of three major continental-scale events in eastern Gondwana: (1) the emplacement of a Silicic Large Igneous Province (LIP) near the continental margin; (2) the volcaniclastic fill, transgression and regression of a major epicontinental seaway developed over at least a quarter of the Australian continent; and (3) epeirogenic uplift, exhumation and continental rupturing culminating in the opening of the Tasman Basin c. 84 Ma. The Whitsunday Silicic LIP event had widespread impact, producing both substantial extrusive volumes of dominantly silicic pyroclastic material and coeval first-cycle volcanogenic sediment that accumulated within many eastern Australian sedimentary basins, and principally in the Great Australian Basin system (>2 Mkm3 combined volume). The final pulse of volcanism and volcanogenic sedimentation at c. 105–95 Ma coincided with epicontinental seaway regression, which shows a lack of correspondence with the global sea-level curve, and alternatively records a wider, continental-scale effect of volcanism and rift tectonism. Widespread igneous underplating related to this LIP event is evident from high paleogeothermal gradients and regional hydrothermal fluid flow detectable in the shallow crust and over a broad region. Enhanced CO2 fluxing through sedimentary basins also records indirectly, large-scale, LIP-related mafic underplating. A discrete episode of rapid crustal cooling and exhumation began c. 100–90 Ma along the length of the eastern Australian margin, related to an enhanced phase of continental rifting that was largely amagmatic, and probably a switch from wide–more narrow rift modes. Along-margin variations in detachment fault architecture produced narrow (SE Australia) and wide continental margins with marginal, submerged continental plateaux (NE Australia). Long-lived NE-trending cross-orogen lineaments controlled the switch from narrow to wide continental margin geometries.

Pulling apart the mid to late Cenozoic magmatic record of the Gulf of California : is there a Comondú arc?

The composition of the lithosphere can be fundamentally altered by long-lived subduction processes such that subduction-modified lithosphere can survive for 100's Myrs. Incorrect petrotectonic interpretations result when spatial-temporal-compositional trends of, and source contributions to, magmatism are not properly considered. Western Mexico has had protracted Cenozoic magmatism developed mostly in-board of active oceanic plate subduction beneath western North America. A broad range of igneous compositions from basalt to high-silica rhyolite were erupted with intermediate to silicic compositions in particular, showing calc-alkaline and other typical subduction-related geochemical signatures. A major Oligocene rhyolitic ignimbrite “flare-up” (>300,000 km3) switched to a bimodal volcanic phase in the Early Miocene (~100,000 km3), associated with distributed extension and opening of numerous grabens. Extension became more focussed ~18 Ma resulting in localised volcanic activity along the future site of the Gulf of California. This localised volcanism (known as the Comondú “arc”) was dominantly effusive and andesite-dacite in composition. Past tectonic interpretations of Comondú-age volcanism may have been incorrect as these regional temporal-compositional changes are alternatively interpreted as a result of increased mixing of mantle-derived basaltic and crust-derived rhyolitic magmas in an active rift environment rather than fluid flux melting of the mantle wedge above the subducting Guadalupe Plate.