Dietary DHA supplementation causes selective changes in phospholipids from different brain regions in both wild type mice and the Tg2576 mouse model of Alzheimer's disease

Alzheimer's disease (AD) is of major concern in ageing populations and we have used the Tg2576 mouse model to understand connections between brain lipids and amyloid pathology. Because dietary docosahexaenoic acid (DHA) has been identified as beneficial, we compared mice fed with a DHA-supplemented diet to those on a nutritionally-sufficient diet. Major phospholipids from cortex, hippocampus and cerebellum were separated and analysed. Each phosphoglyceride had a characteristic fatty acid composition which was similar in cortex and hippocampus but different in the cerebellum. The biggest changes on DHA-supplementation were within ethanolamine phospholipids which, together with phosphatidylserine, had the highest proportions of DHA. Reciprocal alterations in DHA and arachidonate were found. The main diet-induced alterations were found in ethanolamine phospholipids, (and included their ether derivatives), as were the changes observed due to genotype. Tg mice appeared more sensitive to diet with generally lower DHA percentages when on the standard diet and higher relative proportions of DHA when the diet was supplemented. All four major phosphoglycerides analysed showed age-dependent decreases in polyunsaturated fatty acid contents. These data provide, for the first time, a detailed evaluation of phospholipids in different brain areas previously shown to be relevant to behaviour in the Tg2576 mouse model for AD. The lipid changes observed with genotype are consistent with the subtle alterations found in AD patients, especially for the ethanolamine phospholipid molecular species. They also emphasise the contrasting changes in fatty acid content induced by DHA supplementation within individual phospholipid classes

Reflections as a settler person doing research in collaboration with Indigenous peoples.

Objectives To reflect on my position as a settler person in Australia and ensure Indigenous voices are prioritised throughout my research, as part of a co-designed, Aboriginal-led study which aims to understand trends in the removal of Indigenous children born in Western Australia using data linkage and qualitative research. Approach As a non-Indigenous person, it is important to reflect on my cultural background and acknowledge my limited understanding of the cultural context of the Indigenous communities represented in the data. Listening to Indigenous voices and collaborating with Indigenous peoples at all stages of my research – from my PhD supervisor to investigators on the broader study, to members of the community and policy reference groups – will be key to improve my understanding of the data from a system and context I am unfamiliar with. Results Collaboration has been cyclical, with results from the qualitative research and discussion with the reference groups informing the initial quantitative research direction. Findings from this research were presented back to the groups, resulting in further questions and directions to explore. The journey so far has been one of learning and understanding the skills I have and the role they can play whilst acknowledging the limits of my own knowledge and the need for Indigenous voices to guide the research in order to be doing research with Indigenous peoples, rather than on them. Conclusion Co-design with Indigenous peoples is critical for doing research which affects them or uses data from their communities. Understanding my own cultural background and acknowledging the limitations of my experience continues to be important for honest and meaningful collaboration

Phenotype-genotype association grid: a convenient method for summarizing multiple association analyses

BACKGROUND: High-throughput genotyping generates vast amounts of data for analysis; results can be difficult to summarize succinctly. A single project may involve genotyping many genes with multiple variants per gene and analyzing each variant in relation to numerous phenotypes, using several genetic models and population subgroups. Hundreds of statistical tests may be performed for a single SNP, thereby complicating interpretation of results and inhibiting identification of patterns of association. RESULTS: To facilitate visual display and summary of large numbers of association tests of genetic loci with multiple phenotypes, we developed a Phenotype-Genotype Association (PGA) grid display. A database-backed web server was used to create PGA grids from phenotypic and genotypic data (sample sizes, means and standard errors, P-value for association). HTML pages were generated using Tcl scripts on an AOLserver platform, using an Oracle database, and the ArsDigita Community System web toolkit. The grids are interactive and permit display of summary data for individual cells by a mouse click (i.e. least squares means for a given SNP and phenotype, specified genetic model and study sample). PGA grids can be used to visually summarize results of individual SNP associations, gene-environment associations, or haplotype associations. CONCLUSION: The PGA grid, which permits interactive exploration of large numbers of association test results, can serve as an easily adapted common and useful display format for large-scale genetic studies. Doing so would reduce the problem of publication bias, and would simplify the task of summarizing large-scale association studies

Mid-Holocene coastline reconstruction from geomorphological sea level indicators in the Tràng An World Heritage Site, Northern Vietnam

In this paper we present a high resolution palaeo coastline model for the isolated limestone massif of Tràng An, Ninh Bình province, Vietnam. The archaeological and palaeoecological record here comprise rich archives of human activity set within a landscape that was cyclically transformed between inland and archipelagic states under the influence of past sea level changes. These records have become informative proxies in the study of current sea level rise. Well-preserved notches along the vertical limestone cliffs within the study property reveal several phases of prolonged stable sea levels that likely pertain to the Mid-Holocene marine transgression 8 ka BP to 4 ka BP and allow for detailed coastline reconstructions for parts of the Red River Delta (RRD). The resulting coastline model facilitates a closer look at past human responses to landscape and environmental changes at local and individual site-level, which improves our understanding of past human adaptations to climate-change induced sea level rise. These data also stand to inform current coastal vulnerability assessments and climate change response models

Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study

<p>Abstract</p> <p>Background</p> <p>Echocardiographic left ventricular (LV) measurements, exercise responses to standardized treadmill test (ETT) and brachial artery (BA) vascular function are heritable traits that are associated with cardiovascular disease risk. We conducted a genome-wide association study (GWAS) in the community-based Framingham Heart Study.</p> <p>Methods</p> <p>We estimated multivariable-adjusted residuals for quantitative echocardiography, ETT and BA function traits. Echocardiography residuals were averaged across 4 examinations and included LV mass, diastolic and systolic dimensions, wall thickness, fractional shortening, left atrial and aortic root size. ETT measures (single exam) included systolic blood pressure and heart rate responses during exercise stage 2, and at 3 minutes post-exercise. BA measures (single exam) included vessel diameter, flow-mediated dilation (FMD), and baseline and hyperemic flow responses. Generalized estimating equations (GEE), family-based association tests (FBAT) and variance-components linkage were used to relate multivariable-adjusted trait residuals to 70,987 SNPs (Human 100K GeneChip, Affymetrix) restricted to autosomal SNPs with minor allele frequency ≥0.10, genotype call rate ≥0.80, and Hardy-Weinberg equilibrium p ≥ 0.001.</p> <p>Results</p> <p>We summarize results from 17 traits in up to 1238 related middle-aged to elderly men and women. Results of all association and linkage analyses are web-posted at <url>http://ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007</url>. We confirmed modest-to-strong heritabilities (estimates 0.30–0.52) for several Echo, ETT and BA function traits. Overall, p < 10^-5in either GEE or FBAT models were observed for 21 SNPs (nine for echocardiography, eleven for ETT and one for BA function). The top SNPs associated were (GEE results): LV diastolic dimension, rs1379659 (<it>SLIT2</it>, p = 1.17*10^-7); LV systolic dimension, rs10504543 (<it>KCNB2</it>, p = 5.18*10^-6); LV mass, rs10498091 (p = 5.68*10^-6); Left atrial size, rs1935881 (<it>FAM5C</it>, p = 6.56*10^-6); exercise heart rate, rs6847149 (<it>NOLA1</it>, p = 2.74*10^-6); exercise systolic blood pressure, rs2553268 (<it>WRN</it>, p = 6.3*10^-6); BA baseline flow, rs3814219 (<it>OBFC1</it>, 9.48*10^-7), and FMD, rs4148686 (<it>CFTR</it>, p = 1.13*10^-5). Several SNPs are reasonable biological candidates, with some being related to multiple traits suggesting pleiotropy. The peak LOD score was for LV mass (4.38; chromosome 5); the 1.5 LOD support interval included <it>NRG2</it>.</p> <p>Conclusion</p> <p>In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.</p

Atherosclerotic Biomarkers and Aortic Atherosclerosis by Cardiovascular Magnetic Resonance Imaging in the Framingham Heart Study

Background: The relations between subclinical atherosclerosis and inflammatory biomarkers have generated intense interest but their significance remains unclear. We sought to determine the association between a panel of biomarkers and subclinical aortic atherosclerosis in a community‐based cohort. Methods and Results: We evaluated 1547 participants of the Framingham Heart Study Offspring cohort who attended the 7th examination cycle and underwent both cardiovascular magnetic resonance imaging (CMR) and assays for 10 biomarkers associated with atherosclerosis: high‐sensitivity C‐reactive protein, fibrinogen, intercellular adhesion molecule‐1, interleukin‐6, interleukin‐18, lipoprotein‐associated phospholipase‐A2 activity and mass, monocyte chemoattractant protein‐1, P‐selectin, and tumor necrosis factor receptor‐2. In logistic regression analysis, we found no significant association between the biomarker panel and the presence of aortic plaque (global P=0.53). Using Tobit regression with aortic plaque as a continuous variable, we noted a modest association between biomarker panel and aortic plaque volume in age‐ and sex‐adjusted analyses (P=0.003). However, this association was attenuated after further adjustment for clinical covariates (P=0.09). Conclusions: In our community‐based cohort, we found no significant association between our multibiomarker panel and aortic plaque. Our results underscore the strengths and limitations of the use of biomarkers for the identification of subclinical atherosclerosis and the importance of traditional risk factors

Optical vs. infrared studies of dusty galaxies and AGN: (I) Nebular emission lines

Optical nebular emission lines are commonly used to estimate the star formation rate of galaxies and the black hole accretion rate of their central active nucleus. The accuracy of the conversion from line strengths to physical properties depends upon the accuracy to which the lines can be corrected for dust attenuation. For studies of single galaxies with normal amounts of dust, most dust corrections result in the same derived properties within the errors. However, for statistical studies of populations of galaxies, or for studies of galaxies with higher dust contents such as might be found in some classes of "transition" galaxies, significant uncertainty arises from the dust attenuation correction. We compare the strength of the predominantly unobscured mid-IR [NeII]15.5um + [NeIII]12.8um emission lines to the optical H alpha emission lines in four samples of galaxies: (i) ordinary star forming galaxies, (ii) optically selected dusty galaxies, (iii) ULIRGs, (iv) Seyfert 2 galaxies. We show that a single dust attenuation curve applied to all samples can correct H alpha emission for dust attenuation to a factor better than 2. Similarly, we compare mid-IR [OIV] and optical [OIII] luminosities to find that [OIII] can be corrected to a factor better than 3. This shows that the total dust attenuation suffered by the AGN narrow line region is not significantly different to that suffered by the starforming HII regions in the galaxy. We provide explicit dust attenuation corrections, together with errors, for [OII], [OIII] and H alpha. The best-fit average attenuation curve is slightly greyer than the Milky-Way extinction law, indicating either that external galaxies have slightly different typical dust properties to the Milky Way, or that there is a significant contribution from scattering. Finally, we uncover an intriguing correlation between Silicate absorption and Balmer decrement.Comment: 19 pages, 9 figures, accepted for publication in MNRA

Gravity Currents in Aquatic Canopies

A lock exchange experiment is used to investigate the propagation of gravity currents through a random array of rigid, emergent cylinders which represents a canopy of aquatic plants. As canopy drag increases, the propagating front varies from the classic profile of an unobstructed gravity current to a triangular profile. Unlike the unobstructed lock exchange, the gravity current in the canopy decelerates with time as the front lengthens. Two drag-dominated regimes associated with linear and nonlinear drag laws are identified. The theoretical expression for toe velocity is supported by observed values. Empirical criteria are developed to predict the current regime from the cylinder Reynolds number and the array density.National Science Foundation (U.S.) (grant EAR0309188)National Science Foundation (U.S.) (grant EAR0509658)Massachusetts Institute of Technology (Presidential Graduate Fellowship