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    Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA

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    Altered epigenetic mechanisms have been previously reported in growth restricted offspring whose mothers experienced environmental insults during pregnancy in both human and rodent studies. We previously reported changes in the expression of the DNA methyltransferase Dnmt3a and the imprinted genes Cdkn1c (Cyclin-dependent kinase inhibitor 1C) and Kcnq1 (Potassium voltage-gated channel subfamily Q member 1) in the kidney tissue of growth restricted rats whose mothers had uteroplacental insufficiency induced on day 18 of gestation, at both embryonic day 20 (E20) and postnatal day 1 (PN1). To determine the mechanisms responsible for changes in the expression of these imprinted genes, we investigated DNA methylation of KvDMR1, an imprinting control region (ICR) that includes the promoter of the antisense long non-coding RNA Kcnq1ot1 (Kcnq1 opposite strand/antisense transcript 1). Kcnq1ot1 expression decreased by 51% in growth restricted offspring compared to sham at PN1. Interestingly, there was a negative correlation between Kcnq1ot1 and Kcnq1 in the E20 growth restricted group (Spearman’s ρ = 0.014). No correlation was observed between Kcnq1ot1 and Cdkn1c expression in either group at any time point. Additionally, there was a 11.25% decrease in the methylation level at one CpG site within KvDMR1 ICR. This study, together with others in the literature, supports that long non-coding RNAs may mediate changes seen in tissues of growth restricted offspring.</p

    No scientific evidence that Homo naledi buried their dead and produced rock art

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    Here we argue that the evidence presented so far is not compelling enough to support the deliberate burial of the dead by H. naledi nor that they made the purported engravings. Substantial additional documentation and scientific analyses are needed before we can rule out that natural agents and post-depositional processes are responsible for the accumulation of bodies/body parts and to prove the intentional excavation and filling of pits by H. naledi. Moreover, detailed analyses are needed to demonstrate that the so-called ‘engravings’ are indeed human-made marks and that, like the purported evidence of fire use, they can be securely linked to H. naledi. Our commentary also offers a brief insight on the state of the field regarding the importance of responsible social communication and the challenges brought by new models of scientific publication.</p

    Distribution Tails, Recession Risks and Macroeconomic Policies

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    The Global Financial Crisis of 2007–2009 ignited significant reconsideration of financial and economic policies, spurring extensive research efforts to prevent future crises and cultivate a more stable and inclusive economic framework. Our research proposes a macro-financial empirical modelling framework that can assess various short-term and long-term macroeconomic risks through the examination of the tails of distributions of macroeconomic variables. The analysis reveals many novel facts regarding higher moments of the US output growth distribution. It also implies new findings and policy recommendations related to the impact of financial (risk premia) as well as monetary policy shocks on downside macroeconomic risk.</p

    The archaeology of eastern Lutruwita (Tasmania)

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    Fifty years have passed since the first systematic archaeological surveys and excavations were conducted in Lutruwita (Tasmania). Despite numerous Late Pleistocene archaeological discoveries in the southwest region, no indisputable pre-Holocene sites have been found in eastern Tasmania. This profound difference raises questions about how Aboriginal people utilised the Lutruwita landscape; first as a projecting peninsula into the Southern Ocean and then as an island cut off by rising seas c.14000 years ago. To examine the difference between east and west further, legacy data excavated by one of us (RJ) in 1964 at the Oatlands OL1 site and stored at the Tasmanian Museum and Art Gallery (TMAG) has been analysed. The results of pXRF chemical analysis of artefact raw material, radiocarbon dating and studies of faunal remains have produced information that highlights the Holocene interaction between people in eastern Lutruwita. Despite the current lack of Late Pleistocene evidence from eastern Lutruwita, this pattern appears to be different from land use models for Late Pleistocene southwestern Lutruwita. With new information from the OL1 rock shelter site we can now contrast the Late Pleistocene hunting economics with the exceptionally well-preserved faunal remains found in the Holocene site, OL1.</p

    Simulating Microfluidic Flow Focusing Droplet Generation Under Surface Tension, Geometric, and Adhesive Variation, and Refining Dynamic Simulated Adhesion

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    A thesis submitted in total fulfillment of the requirements for the degree of Master of Science to the School of Computing, Engineering and Mathematical Sciences, La Trobe University, Victoria, Australia.</p

    In need of improvement: archaeological evidence of river management in South-Eastern Australia

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    Patterns of river modification since settler invasion of southern Australia are the product of a specific set of deep-seated and implicit cultural values concerning the purpose and function of waterways. Rivers have been dammed, diverted, dredged and straightened to meet a range of human needs and objectives. Such changes are routinely described as ‘improvements’ but there is a lack of critical engagement with what ‘improvement’ might mean. Interventions carried out initially on an ad hoc basis, and later more systematically with state support, collectively shed light on the persistent underlying drive to ‘Improve’ nature and society that has permeated Western thought since the Enlightenment. Here we use the example of one river system, the Loddon, to analyse ways in which Improvement intersected with settler engagement with Australian rivers. We argue that settler interventions have been informed by a consistent set of understandings about the purpose of rivers. The characteristics of water management infrastructure along the Loddon reveal how the river fell short of the settler-colonial ideal and why they thought it needed to be Improved at all.</p

    Characterisation of novel influenza‐derived HLA‐B*18:01‐restricted epitopes

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    Objectives: Seasonal influenza viruses cause roughly 650 000 deaths annually despite available vaccines. CD8+ T cells typically recognise influenza-derived peptides from internal structural and non-structural influenza proteins and are an attractive avenue for future vaccine design as they could reduce the severity of disease following infection with diverse influenza strains. CD8+ T cells recognise peptides presented by the highly polymorphic Human Leukocyte Antigens class I molecules (HLA-I). Each HLA-I variant has distinct peptide binding preferences, representing a significant obstacle for designing vaccines that elicit CD8+ T cell responses across broad populations. Consequently, the rational design of a CD8+ T cell-mediated vaccine would require the identification of highly immunogenic peptides restricted to a range of different HLA molecules. Methods: Here, we assessed the immunogenicity of six recently published novel influenza-derived peptides identified by mass-spectrometry and predicted to bind to the prevalent HLA-B*18:01 molecule. Results: Using CD8+ T cell activation assays and protein biochemistry, we showed that 3/6 of the novel peptides were immunogenic in several HLA-B*18:01+ individuals and confirmed their HLA-B*18:01 restriction. We subsequently compared CD8+ T cell responses towards the previously identified highly immunogenic HLA-B*18:01-restricted NP219 peptide. Using X-ray crystallography, we solved the first crystal structures of HLA-B*18:01 presenting immunogenic influenza-derived peptides. Finally, we dissected the first TCR repertoires specific for HLA-B*18:01 restricted pathogen-derived peptides, identifying private and restricted repertoires against each of the four peptides. Conclusion: Overall the characterisation of these novel immunogenic peptides provides additional HLA-B*18:01-restricted vaccine targets derived from the Matrix protein 1 and potentially the non-structural protein and the RNA polymerase catalytic subunit of influenza viruses.</p

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