Redating the earliest evidence of the mid-Holocene relative sea-level highstand in Australia and implications for global sea-level rise.

Reconstructing past sea levels can help constrain uncertainties surrounding the rate of change, magnitude, and impacts of the projected increase through the 21st century. Of significance is the mid-Holocene relative sea-level highstand in tectonically stable and remote (far-field) locations from major ice sheets. The east coast of Australia provides an excellent arena in which to investigate changes in relative sea level during the Holocene. Considerable debate surrounds both the peak level and timing of the east coast highstand. The southeast Australian site of Bulli Beach provides the earliest evidence for the establishment of a highstand in the Southern Hemisphere, although questions have been raised about the pretreatment and type of material that was radiocarbon dated for the development of the regional sea-level curve. Here we undertake a detailed morpho- and chronostratigraphic study at Bulli Beach to better constrain the timing of the Holocene highstand in eastern Australia. In contrast to wood and charcoal samples that may provide anomalously old ages, probably due to inbuilt age, we find that short-lived terrestrial plant macrofossils provide a robust chronological framework. Bayesian modelling of the ages provide improved dating of the earliest evidence for a highstand at 6,880±50 cal BP, approximately a millennium later than previously reported. Our results from Bulli now closely align with other sea-level reconstructions along the east coast of Australia, and provide evidence for a synchronous relative sea-level highstand that extends from the Gulf of Carpentaria to Tasmania. Our refined age appears to be coincident with major ice mass loss from Northern Hemisphere and Antarctic ice sheets, supporting previous studies that suggest these may have played a role in the relative sea-level highstand. Further work is now needed to investigate the environmental impacts of regional sea levels, and refine the timing of the subsequent sea-level fall in the Holocene and its influence on coastal evolution

A Decline in p38 MAPK Signaling Underlies Immunosenescence in Caenorhabditis elegans

The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging in Caenorhabditis elegans, intestinal tissue deterioration and the increased intestinal proliferation of bacteria are observed, but how innate immunity changes during C. elegans aging has not been defined. Here we show that C. elegans exhibits increased susceptibility to bacterial infection with age, and we establish that aging is associated with a decline in the activity of the conserved PMK-1 p38 mitogen-activated protein kinase pathway, which regulates innate immunity in C. elegans. Our data define the phenomenon of innate immunosenescence in C. elegans in terms of the age-dependent dynamics of the PMK-1 innate immune signaling pathway, and they suggest that a cycle of intestinal tissue aging, immunosenescence, and bacterial proliferation leads to death in aging C. elegans

Alcohol, tobacco and illicit drug use amongst same-sex attracted women: results from the Western Australian Lesbian and Bisexual Women's Health and Well-Being Survey

Background: The prevalence of alcohol, tobacco and illicit drug use has been reported to be higheramongst lesbian and bisexual women (LBW) than their heterosexual counterparts. However, few studieshave been conducted with this population in Australia and rates that have been reported vary considerably.Methods: A self-completed questionnaire exploring a range of health issues was administered to 917women aged 15-65 years (median 34 years) living in Western Australia, who identified as lesbian orbisexual, or reported having sex with another woman. Participants were recruited from a range of settings,including Perth Pride Festival events (67.0%, n = 615), online (13.2%, n = 121), at gay bars and nightclubs(12.9%, n = 118), and through community groups (6.9%, n = 63). Results were compared against availablestate and national surveillance data.Results: LBW reported consuming alcohol more frequently and in greater quantities than women in thegeneral population. A quarter of LBW (25.7%, n = 236) exceeded national alcohol guidelines by consumingmore than four standard drinks on a single occasion, once a week or more. However, only 6.8% (n = 62)described themselves as a heavy drinker, suggesting that exceeding national alcohol guidelines may be anormalised behaviour amongst LBW. Of the 876 women who provided data on tobacco use, 28.1% (n =246) were smokers, nearly double the rate in the female population as a whole. One third of the sample(33.6%, n = 308) reported use of an illicit drug in the previous six months. The illicit drugs most commonlyreported were cannabis (26.4%, n = 242), meth/amphetamine (18.6%, n = 171), and ecstasy (17.9%, n =164). Injecting drug use was reported by 3.5% (n = 32) of participants.Conclusion: LBW appear to use alcohol, tobacco and illicit drugs at higher rates than women generally,indicating that mainstream health promotion messages are not reaching this group or are not perceivedas relevant. There is an urgent need for public health practitioners working in the area of substance useto recognise that drug consumption and use patterns of LBW are likely to be different to the widerpopulation and that special considerations and strategies are required to address the unique and complexneeds of this population

Understandings of cervical screening in sexual minority women: A Q-methodological study

Discursive perspectives argue that cervical screening carries social and moral meaning. Overlooked by research into the health needs of sexual minority women, previous literature that has examined uptake of cervical screening has instead targeted increasing attendance via information and service provision. In order to explore the diversity of meanings that British sexual minority women have about cervical screening, the Q-sorts of 34 sexual minority women were factor analysed by-person and rotated to simple structure using Varimax. The five factors are interpreted and discussed relative to competing discourses on information provision within cervical screening. The five accounts are labelled 'cervical screening is': an essential health check that women have the right to refuse; a woman's health entitlement; a vital test but degrading experience; a sensible thing to do; and an unnecessary imposition for some women. Critical approaches to informed choice are explored with attention to recent developments in cervical cancer prevention. Findings highlighting the need for affirmation of diversity within healthcare are considered in relation to existing criteria for UK national screening programmes

An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency.

The ability of cancer cells to establish lethal metastatic lesions requires the survival and expansion of single cancer cells at distant sites. The factors controlling the clonal growth ability of individual cancer cells remain poorly understood. Here, we show that high expression of the transcription factor ARNTL2 predicts poor lung adenocarcinoma patient outcome. Arntl2 is required for metastatic ability in vivo and clonal growth in cell culture. Arntl2 drives metastatic self-sufficiency by orchestrating the expression of a complex pro-metastatic secretome. We identify Clock as an Arntl2 partner and functionally validate the matricellular protein Smoc2 as a pro-metastatic secreted factor. These findings shed light on the molecular mechanisms that enable single cancer cells to form allochthonous tumors in foreign tissue environments

Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis.

Lung cancer is the leading cause of cancer deaths worldwide, with the majority of mortality resulting from metastatic spread. However, the molecular mechanism by which cancer cells acquire the ability to disseminate from primary tumors, seed distant organs, and grow into tissue-destructive metastases remains incompletely understood. We combined tumor barcoding in a mouse model of human lung adenocarcinoma with unbiased genomic approaches to identify a transcriptional program that confers metastatic ability and predicts patient survival. Small-scale in vivo screening identified several genes, including Cd109, that encode novel pro-metastatic factors. We uncovered signaling mediated by Janus kinases (Jaks) and the transcription factor Stat3 as a critical, pharmacologically targetable effector of CD109-driven lung cancer metastasis. In summary, by coupling the systematic genomic analysis of purified cancer cells in distinct malignant states from mouse models with extensive human validation, we uncovered several key regulators of metastatic ability, including an actionable pro-metastatic CD109-Jak-Stat3 axis