201 research outputs found

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    Evolutionary genomics of Chlamydomonas

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    The unicellular green alga Chlamydomonas reinhardtii is one of the primary model organisms in plant and algal biology. Although the species is fundamental to several research areas, including the study of photosynthesis, cilia and the cell cycle, very little is known about its evolutionary biology. Furthermore, C. reinhardtii research is generally limited to a single line of laboratory strains and no genomic resources exist for any closely related species. Consequently, the species has predominantly been studied in isolation, from both a population and phylogenetic perspective. In this thesis, I explore several aspects of the evolutionary genomics of C. reinhardtii and its closest relatives in the genus Chlamydomonas. I use population genomics approaches to characterise population structure across all known C. reinhardtii field isolates, presenting some of the first insights into the evolutionary ecology of the species. I use long read sequencing technology to produce highly contiguous genome assemblies for the three closest relatives of C. reinhardtii. Using these comparative resources, I describe several novel features of Chlamydomonas genomics, including the putative centromeric repeat. I present near complete reference assemblies for two laboratory strains of C. reinhardtii, characterising structural mutations that have occurred in the laboratory and revealing numerous misassemblies in previous versions. Finally, I present an exhaustively curated library of C. reinhardtii transposable elements and I describe a major new clade of retrotransposons present across the green lineage and animals. This collective work greatly expands our understanding of Chlamydomonas evolutionary genomics and is expected to be integral to the continued development of C. reinhardtii as a model for evolutionary biology research

    Outbound Medical Tourism from Mongolia: a Qualitative Examination of Proposed Domestic Health System and Policy Responses to this Trend

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    Background: Medical tourism is the practice of traveling across international boundaries in order to access medical care. Residents of low-to-middle income countries with strained or inadequate health systems have long traveled to other countries in order to access procedures not available in their home countries and to take advantage of higher quality care elsewhere. In Mongolia, for example, residents are traveling to China, Japan, Thailand, South Korea, and other countries for care. As a result of this practice, there are concerns that travel abroad from Mongolia and other countries risks impoverishing patients and their families.   Methods: In this paper, we present findings from 15 interviews with Mongolian medical tourism stakeholders about the impacts of, causes of, and responses to outbound medical tourism. These findings were developed using a case study methodology that also relied on tours of health care facilities and informal discussions with citizens and other stakeholders during April, 2012.   Results: Based on these findings, health policy changes are needed to address the outflow of Mongolian medical tourists. Key areas for reform include increasing funding for the Mongolian health system and enhancing the efficient use of these funds, improving training opportunities and incentives for health workers, altering the local culture of care to be more supportive of patients, and addressing concerns of corruption and favouritism in the health system.   Conclusions: While these findings are specific to the Mongolian health system, other low-to-middle income countries experiencing outbound medical tourism will benefit from consideration of how these findings apply to their own contexts. As medical tourism is increasing in visibility globally, continued research on its impacts and context-specific policy responses are needed. &nbsp

    Systematic calibration error requirements for gravitational-wave detectors via the Cramér-Rao bound

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    Gravitational-wave (GW) laser interferometers such as Advanced LIGO (The LIGO Scientific Collaboration 2015 Class. Quantum Grav. 32 074001) transduce spacetime strain into optical power fluctuation. Converting this optical power fluctuation back into an estimated spacetime strain requires a calibration process that accounts for both the interferometer's optomechanical response and the feedback control loop used to control the interferometer test masses. Systematic errors in the calibration parameters lead to systematic errors in the GW strain estimate, and hence to systematic errors in the astrophysical parameter estimates in a particular GW signal. In this work we examine this effect for a GW signal similar to GW150914, both for a low-power detector operation similar to the first and second Advanced LIGO observing runs and for a higher-power operation with detuned signal extraction. We set requirements on the accuracy of the calibration such that the astrophysical parameter estimation is limited by errors introduced by random detector noise, rather than calibration systematics. We also examine the impact of systematic calibration errors on the possible detection of a massive graviton

    Architecture and evolution of subtelomeres in the unicellular green alga Chlamydomonas reinhardtii

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    International audienceIn most eukaryotes, subtelomeres are dynamic genomic regions populated by multi-copy sequences of different origins, which can promote segmental duplications and chromosomal rearrangements. However, their repetitive nature has complicated the efforts to sequence them, analyse their structure and infer how they evolved. Here, we use recent genome assemblies of Chlamydomonas reinhardtii based on long-read sequencing to comprehensively describe the subtelomere architecture of the 17 chromosomes of this model unicellular green alga. We identify three main repeated elements present at subtelomeres, which we call Sultan, Subtile and Suber, alongside three chromosome extremities with ribosomal DNA as the only identified component of their subtelomeres. The most common architecture, present in 27 out of 34 subtelomeres, is a heterochromatic array of Sultan elements adjacent to the telomere, followed by a transcribed Spacer sequence, a G-rich microsatellite and transposable elements. Sequence similarity analyses suggest that Sultan elements underwent segmental duplications within each subtelomere and rearranged between subtelomeres at a much lower frequency. Analysis of other green algae reveals species-specific repeated elements that are shared across subtelomeres, with an overall organization similar to C. reinhardtii. This work uncovers the complexity and evolution of subtelomere architecture in green algae

    Predictors of mortality and disability in stroke-associated pneumonia

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    Whilst stroke-associated pneumonia (SAP) is common and associated with poor outcomes, less is known about the determinants of these adverse clinical outcomes in SAP. To identify the factors that influence mortality and morbidity in SAP. Data for patients with SAP (n = 854) were extracted from a regional Hospital Stroke Register in Norfolk, UK (2003-2015). SAP was defined as pneumonia occurring within 7 days of admission by the treating clinicians. Mutlivariable regression models were constructed to assess factors influencing survival and the level of disability at discharge using modified Rankin Scale [mRS]. Mean (SD) age was 83.0 (8.7) years and ischaemic stroke occurred in 727 (85.0%). Mortality was 19.0% at 30 days and 44.0% at 6 months. Stroke severity assessment using National Institutes of Health Stroke Scale was not recorded in the data set although Oxfordshire Community Stroke Project was Classification. In the multivariable analyses, 30-day mortality was independently associated with age (OR 1.04, 95% CI 1.01-1.07, p = 0.01), haemorrhagic stroke (2.27, 1.07-4.78, p = 0.03) and pre-stroke disability (mRS 4-5 v 0-1: 6.45, 3.12-13.35, p < 0.001). 6-month mortality was independently associated with age (< 0.001), pre-stroke disability (p < 0.001) and certain comorbidities, including the following: dementia (6.53, 4.73-9.03, p < 0.001), lung cancer (2.07, 1.14-3.77, p = 0.017) and previous transient ischemic attack (1.94, 1.12-3.36, p = 0.019). Disability defined by mRS at discharge was independently associated with age (1.10, 1.05-1.16, p < 0.001) and plasma C-reactive protein (1.02, 1.01-1.03, p = 0.012). We have identified non-modifiable determinants of poor prognosis in patients with SAP. Further studies are required to identify modifiable factors which may guide areas for intervention to improve the prognosis in SAP in these patients

    Insights into Platypus Population Structure and History from Whole-Genome Sequencing

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    The platypus is an egg-laying mammal which, alongside the echidna, occupies a unique place in the mammalian phylogenetic tree. Despite widespread interest in its unusual biology, little is known about its population structure or recent evolutionary history. To provide new insights into the dispersal and demographic history of this iconic species, we sequenced the genomes of 57 platypuses from across the whole species range in eastern mainland Australia and Tasmania. Using a highly improved reference genome, we called over 6.7 M SNPs, providing an informative genetic data set for population analyses. Our results show very strong population structure in the platypus, with our sampling locations corresponding to discrete groupings between which there is no evidence for recent gene flow. Genome-wide data allowed us to establish that 28 of the 57 sampled individuals had at least a third-degree relative among other samples from the same river, often taken at different times. Taking advantage of a sampled family quartet, we estimated the de novo mutation rate in the platypus at 7.0 × 10−9/bp/generation (95% CI 4.1 × 10−9–1.2 × 10−8/bp/generation). We estimated effective population sizes of ancestral populations and haplotype sharing between current groupings, and found evidence for bottlenecks and long-term population decline in multiple regions, and early divergence between populations in different regions. This study demonstrates the power of whole-genome sequencing for studying natural populations of an evolutionarily important species.We thank the High-Throughput Genomics Group at the Wellcome Centre for Human Genetics (funded by Wellcome Trust grant reference 090532/Z/09/Z) for the generation of sequencing data. This work was supported by a Wellcome Trust Core Award (090532/Z/09/Z) to P.D. and by a University of Sydney StartUp Research grant to J.G
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