Detecting human impacts on the flora, fauna, and summer monsoon of Pleistocene Australia

International audienceAll of Australia's largest mammalian vertebrates became extinct 50 to 45 ka (thousand years ago), shortly after human colonization. Between 60 and 40 ka Australian climate was similar to present and not changing rapidly. Consequently, attention has turned toward plausible human mechanisms for the extinction, with proponents for over-hunting, ecosystem change, and introduced disease. To differentiate between these options we utilize isotopic tracers of diet preserved in eggshells of two large, flightless birds to track the status of ecosystems before and after human colonization. ?13C preserved in their eggshells monitor a bird's dietary intake in the weeks to months before egg-laying. More than 500 dated eggshells from central Australia of the Australian emu (Dromaius novaehollandiae), an opportunistic, dominantly herbivorous feeder, provide a continuous 140 kyr dietary ? 13C reconstruction. More than 350 dated eggshells from the same region of the heavier, extinct, giant bird Genyornis newtoni define its dietary intake from 140 ka until its extinction about 50 ka. Additional dietary records for both species were developed from two distant regions. Dromaius eggshell dietary ?13C reveals an unprecedented reduction in the bird's food resources about 50 ka, coeval in all three regions, suggesting conversion at that time of a tree/shrub savannah with occasionally rich grasslands to the modern desert scrub. We speculate that ecosystem collapse across the arid and semi-arid zones is a consequence of systematic burning by early humans. Genyornis diet everywhere is more restricted than in co-existing Dromaius, implying a more specialized feeding strategy. These data suggest that generalist feeders, such as Dromaius, were able to adapt to a changed vegetation regime, whereas more specialized feeders, such as Genyornis, became extinct. The altered vegetation may have also impacted Australian climate. Changes in the strength of climate feedbacks linked to vegetation and soil type (moisture recycling, surface roughness, albedo) may have weakened the penetration of monsoon moisture into the continental interior under the new ecosystem. Climate modeling suggests such a shift may have reduced monsoon rain in the interior by as much as 50%

A dedicated greedy pursuit algorithm for sparse spectral representation of music sound

A dedicated algorithm for sparse spectral representation of music sound is presented. The goal is to enable the representation of a piece of music signal as a linear superposition of as few spectral components as possible, without affecting the quality of the reproduction. A representation of this nature is said to be sparse. In the present context sparsity is accomplished by greedy selection of the spectral components, from an overcomplete set called a dictionary. The proposed algorithm is tailored to be applied with trigonometric dictionaries. Its distinctive feature being that it avoids the need for the actual construction of the whole dictionary, by implementing the required operations via the fast Fourier transform. The achieved sparsity is theoretically equivalent to that rendered by the orthogonal matching pursuit (OMP) method. The contribution of the proposed dedicated implementation is to extend the applicability of the standard OMP algorithm, by reducing its storage and computational demands. The suitability of the approach for producing sparse spectral representation is illustrated by comparison with the traditional method, in the line of the short time Fourier transform, involving only the corresponding orthonormal trigonometric basis

Dealing with climate change through understanding tropical ocean-atmosphere climate interactions and their impacts on marine ecosystems.

Australian scientists are world leaders in developing robust palaeo-environmental reconstructions from coral archives, relevant for understanding Australian climate extremes. The key issues for advancing this field are the need for high-resolution marine paleoclimate records to place the present in the context of past natural climate and sea level change, and to understand the impact of those changes on marine ecosystems. We call for sustained investment in paleoclimate science, infrastructure, and personnel to advance these critical areas of research

Inter-hemispheric linkages in climate change: Paleo-perspectives for future climate change

The Pole-Equator-Pole (PEP) projects of the PANASH (Paleoclimates of the Northern and Southern Hemisphere) programme have significantly advanced our understanding of past climate change on a global basis and helped to integrate paleo-science across regions and research disciplines. PANASH science allows us to constrain predictions for future climate change and to contribute to the management of consequent environmental changes. We identify three broad areas where PEP science makes key contributions. 1. The pattern of global changes. Knowing the exact timing of glacial advances (synchronous or otherwise) during the last glaciation is critical to understanding interhemispheric links in climate. Work in PEPI demonstrated that the tropical Andes in South America were deglaciated earlier than the Northern Hemisphere (NH) and that an extended warming began there ca. 21 000 cal years BP. The general pattern is consistent with Antarctica and has now been replicated from studies in Southern Hemisphere (SH) regions of the PEPII transect. That significant deglaciation of SH alpine systems and Antarctica led deglaciation of NH ice sheets may reflect either i) faster response times in alpine systems and Antarctica, ii) regional moisture patterns that influenced glacier mass balance, or iii) a SH temperature forcing that led changes in the NH. This highlights the limitations of current understanding and the need for further fundamental paleoclimate research. 2. Changes in modes of operation of oscillatory climate systems. Work across all the PEP transects has led to the recognition that the El Nino Southern Oscillation (ENSO) phenomenon has changed markedly through time. It now appears that ENSO operated during the last glacial termination and during the early Holocene, but that precipitation teleconnections even within the Pacific Basin were turned down, or off. In the modern ENSO phenomenon both inter-annual and seven year periodicities are present, with the inter-annual signal dominant. Paleo-data demonstrate that the relative importance of the two periodicities changes through time, with longer periodicities dominant in the early Holocene. 3. The recognition of climate modulation of oscillatory systems by climate events. We examine the relationship of ENSO to a SH climate event, the Antarctic cold reversal (ACR), in the New Zealand region. We demonstrate that the onset of the ACR was associated with the apparent switching on of an ENSO signal in New Zealand. We infer that this related to enhanced zonal SW winds with the amplification of the pressure fields allowing an existing but weak ENSO signal to manifest itself. Teleconnections of this nature would be difficult to predict for future abrupt change as boundary conditions cannot readily be specified. Paleo-data are critical to predicting the teleconnections of future changes

The next frontier: Fostering innovation by improving health data access and utilization

Beneath most lively policy debates sit dry-as-dust theoretical and methodological discussions. Current disputes over the EU Adaptive Pathways initiative and the proposed US 21st Century Cures Act may ultimately rest on addressing arcane issues of data curation, standardization, and utilization. Improved extraction of inform ation on the safety and effectiveness of drugs-in-use must parallel adjustments in evidence requirements at the time of licensing. To do otherwise may compromise safety and efficacy in the name of fostering innovation

RXR ligands negatively regulate thrombosis and hemostasis

OBJECTIVE: Platelets have been found to express intracellular nuclear receptors including the Retinoid X receptors (RXRα and RXRβ). Treatment of platelets with ligands of RXR has been shown to inhibit platelet responses to ADP and thromboxane A2, however the effects on responses to other platelet agonists as well as the underlying mechanism has not been fully characterised. APPROACH AND RESULTS: The effect of 9-cis-retinoic acid (9-cis-RA), docosahexaenoic acid and synthetic ligand for RXR, methoprene acid on collagen receptor (GPVI) agonists and Thrombin stimulated platelet function; including aggregation, granule secretion, integrin activation, calcium mobilisation, integrin αIIbβ3 outside-in signalling and thrombus formation in vitro and in vivo were determined. Treatment of platelets with RXR ligands resulted in attenuation of platelet functional responses following stimulation by GPVI agonists and thrombin and inhibition of integrin αIIbβ3 outside-in signalling. Treatment with 9-cis-RA caused inhibition of thrombus formation in vitro and an impairment of thrombosis and haemostasis in vivo. Both RXR ligands stimulated protein kinase A activation, measured by VASP S157 phosphorylation, that was found to be dependent on both cAMP and NFκB activity. CONCLUSIONS: This study identifies a widespread, negative regulatory role for RXR in the regulation of platelet functional responses and thrombus formation and describes novel events that lead to the upregulation of PKA, a known negative regulator of many aspects of platelet function. This mechanism may offer a possible explanation for the cardioprotective effects described in vivo following treatment with RXR ligands

Novel Mechanism of Attenuation of LPS-Induced NF-Kappab Activation by the Heat Shock Protein 90 Inhibitor, 17-N-Allylamino-17-Demethoxygeldanamycin, in Human Lung Microvascular Endothelial Cells

Heat shock protein (hsp) 90 inhibition attenuates NF-kappaB activation and blocks inflammation. However, the precise mechanism of NF-kappaB regulation by hsp90 in the endothelium is not clear. We investigated the mechanisms of hsp90 inhibition by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) on NF-kappaB activation by LPS in primary human lung microvascular endothelial cells. Transcriptional activation of NF-kappaB was measured by luciferase reporter assay, gene expression by real-time RT-PCR, DNA binding of transcription factors by chromatin immunoprecipitation assay, protein-protein interaction by coimmunoprecipitation/immunoblotting, histone deacetylase (HDAC)/histone acetyltransferase enzyme activity by fluorometry, and nucleosome eviction by partial microccocal DNase digestion. In human lung microvascular endothelial cells, 17-AAG-induced degradation of IKBalpha was accomplished regardless of the phosphorylation/ubiquitination state of the protein. Hence, 17-AAG did not block LPS-induced NF-kappaB nuclear translocation and DNA binding activity. Instead, 17-AAG blocked the recruitment of the coactivator, cAMP response element binding protein binding protein, and prevented the assembly of a transcriptionally competent RNA polymerase II complex at the kappaB elements of the IKBalpha (an NF-kappaB-responsive gene) promoter. The effect of LPS on IKBalpha mRNA expression was associated with rapid deacetylation of histone-H3(Lys9) and a dramatic down-regulation of core histone H3 binding. Even though treatment with an HDAC inhibitor produced the same effect as hsp90 inhibition, the effect of 17-AAG was independent of HDAC. We conclude that hsp90 inhibition attenuates NF-kappaB transcriptional activation by preventing coactivator recruitment and nucleosome eviction from the target promoter in human lung endothelial cells

Dealing with Climate Change: Paleoclimate research in Australia

Palaeoclimate research relevant to marine systems in Australia includes the collection and analysis of: (a) shallow-water and deep-sea corals, which provide highresolution archives, (b) deep-sea sediment and ice cores, which span longer time scales, and (c) palaeoclimate modelling, which gives us insights into mechanisms, dynamics and thresholds underlying past climate states. Palaeoclimate research in Australia is mature and well recognised internationally. To further advance Australian palaeoclimate research, we must address major challenges that include insufficient research vessel access, insufficient targeted research funding, as well as the lack of a well funded national centre to coordinate research efforts (e.g. academic institution or ARC Centre of Excellence for Palaeoclimate Research)

Whole genome single nucleotide polymorphism based phylogeny of Francisella tularensis and its application to the development of a strain typing assay

<p>Abstract</p> <p>Background</p> <p>A low genetic diversity in <it>Francisella tularensis </it>has been documented. Current DNA based genotyping methods for typing <it>F. tularensis </it>offer a limited and varying degree of subspecies, clade and strain level discrimination power. Whole genome sequencing is the most accurate and reliable method to identify, type and determine phylogenetic relationships among strains of a species. However, lower cost typing schemes are necessary in order to enable typing of hundreds or even thousands of isolates.</p> <p>Results</p> <p>We have generated a high-resolution phylogenetic tree from 40 <it>Francisella </it>isolates, including 13 <it>F. tularensis </it>subspecies <it>holarctica </it>(type B) strains, 26 <it>F. tularensis </it>subsp. <it>tularensis </it>(type A) strains and a single <it>F. novicida </it>strain. The tree was generated from global multi-strain single nucleotide polymorphism (SNP) data collected using a set of six Affymetrix GeneChip^®resequencing arrays with the non-repetitive portion of LVS (type B) as the reference sequence complemented with unique sequences of SCHU S4 (type A). Global SNP based phylogenetic clustering was able to resolve all non-related strains. The phylogenetic tree was used to guide the selection of informative SNPs specific to major nodes in the tree for development of a genotyping assay for identification of <it>F. tularensis </it>subspecies and clades. We designed and validated an assay that uses these SNPs to accurately genotype 39 additional <it>F. tularensis </it>strains as type A (A1, A2, A1a or A1b) or type B (B1 or B2).</p> <p>Conclusion</p> <p>Whole-genome SNP based clustering was shown to accurately identify SNPs for differentiation of <it>F. tularensis </it>subspecies and clades, emphasizing the potential power and utility of this methodology for selecting SNPs for typing of <it>F. tularensis </it>to the strain level. Additionally, whole genome sequence based SNP information gained from a representative population of strains may be used to perform evolutionary or phylogenetic comparisons of strains, or selection of unique strains for whole-genome sequencing projects.</p