SummaryDietary InsP6 can modulate eukaryotic cell proliferation and has complex nutritive consequences, but its metabolism in the mammalian gastrointestinal tract is poorly understood. Therefore, we performed phylogenetic analyses of the gastrointestinal microbiome in order to search for candidate InsP6 phosphatases. We determined that prominent gut bacteria express homologs of the mammalian InsP6 phosphatase (MINPP) and characterized the enzyme from Bacteroides thetaiotaomicron (BtMinpp). We show that BtMinpp has exceptionally high catalytic activity, which we rationalize on the basis of mutagenesis studies and by determining its crystal structure at 1.9 Å resolution. We demonstrate that BtMinpp is packaged inside outer membrane vesicles (OMVs) protecting the enzyme from degradation by gastrointestinal proteases. Moreover, we uncover an example of cross-kingdom cell-to-cell signaling, showing that the BtMinpp-OMVs interact with intestinal epithelial cells to promote intracellular Ca2+ signaling. Our characterization of BtMinpp offers several directions for understanding how the microbiome serves human gastrointestinal physiology.

Aggregation of the pre-synaptic protein, α-synuclein (α-syn), is the key etiological factor in Parkinson's disease (PD) and other alpha-synucleinopathies, such as multiple system atrophy (MSA) and Dementia with Lewy bodies (DLB). Various triggers for pathological α-syn aggregation have been elucidated, including post-translational modifications, oxidative stress, and binding of metal ions, such as calcium. Raised neuronal calcium levels in PD may occur due to mitochondrial dysfunction and/or may relate to calcium channel dysregulation or the reduced expression of the neuronal calcium buffering protein, calbindin-D28k. Recent results on human tissue and a mouse oxidative stress model show that neuronal calbindin-D28k expression excludes α-syn inclusion bodies. Previously, cell culture model studies have shown that transient increases of intracellular free Ca(II), such as by opening of the voltage-gated plasma calcium channels, could induce cytoplasmic aggregates of α-syn. Raised intracellular free calcium and oxidative stress also act cooperatively to promote α-syn aggregation. The association between raised neuronal calcium, α-syn aggregation, oxidative stress, and neurotoxicity is reviewed in the context of neurodegenerative α-syn disease and potential mechanism-based therapies.

The results of an I‐ and Z‐band survey and infrared follow‐up of 1.1 deg2 of the Pleiades open cluster complete to I≈ 21.4 (Ic∼ 22) are presented. A total of 23 candidate cluster members has been unearthed, 15 of which are previously unpublished. Assuming canonical cluster age and distance, and using the latest theoretical models, we determine that the cluster mass function continues to rise down to a mass of 0.03 M⊙, following a power law with α= 0.8. By considering several potential sources of uncertainty we show that this result is robust and we compare it with the results from other work on young clusters.

Abstract. We have compiled the largest magnitude limited sample of candidate substellar Pleiads to date. We fit King profiles to their spatial distribution to determine the Pleiades brown dwarf core radius to be r c == 2.22~~:~~o. Subsequently we have used our improved spatial model to place stringent limits on the shape of the cluster mass function across and below the stellar/substellar regime. We find this to be a power law with index a == 0.41±0.08 (0.3M 0~M~0 .035M 0 ) . Extrapolation of this mass function to M== 0.012M 0 indicates that brown dwarfs contribute only rv 2% to the total mass of the cluster hence we conclude that brown dwarfs do not contribute significantly to disk dark matter.

In 2015–2016, the Clarence Valley in Northern New South Wales, Australia, experienced an unexpectedly high number of deaths by suicide, and the resulting distress was exacerbated by unhelpful press coverage. The local response was to adopt a community-wide positive mental health and wellbeing initiative. This paper describes the process and achievements of the initiative called ‘Our Healthy Clarence’. Key stakeholders were interviewed at year two and relevant documents reviewed. Data were analysed using document and thematic analysis. Our Healthy Clarence was established following community consultation, including forums, interviews, surveys and workshops. It adopted a strengths-based approach to suicide prevention, encompassing positive health promotion, primary and secondary prevention activities, advocacy, and cross-sectoral collaboration. A stakeholder group formed to develop and enact a community mental health and wellbeing plan. Factors contributing to its successful implementation included a collective commitment to mental health and wellbeing, clarity of purpose, leadership support from key local partners, a paid independent coordinator, and inclusive and transparent governance. Stakeholders reported increased community agency, collaboration, optimism and willingness to discuss mental health, suicide and help-seeking. Our Healthy Clarence draws ideas from mental health care, community development and public health. This initiative could serve as a model for other communities to address suicide, self-harm and improve wellbeing on a whole-of-community scale.