49 research outputs found
Antarctic penguin response to habitat change as Earth's troposphere reaches 2°C above preindustrial levels
Author Posting. © Ecological Society of America, 2010. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Ecological Monographs 80 (2010): 49–66, doi:10.1890/08-2289.1.We assess the response of pack ice penguins, Emperor (Aptenodytes forsteri) and Adélie (Pygoscelis adeliae), to habitat variability and, then, by modeling habitat alterations, the qualitative changes to their populations, size and distribution, as Earth's average tropospheric temperature reaches 2°C above preindustrial levels (ca. 1860), the benchmark set by the European Union in efforts to reduce greenhouse gases. First, we assessed models used in the Intergovernmental Panel on Climate Change Fourth Assessment Report (AR4) on penguin performance duplicating existing conditions in the Southern Ocean. We chose four models appropriate for gauging changes to penguin habitat: GFDL-CM2.1, GFDL-CM2.0, MIROC3.2(hi-res), and MRI-CGCM2.3.2a. Second, we analyzed the composited model ENSEMBLE to estimate the point of 2°C warming (2025–2052) and the projected changes to sea ice coverage (extent, persistence, and concentration), sea ice thickness, wind speeds, precipitation, and air temperatures. Third, we considered studies of ancient colonies and sediment cores and some recent modeling, which indicate the (space/time) large/centennial-scale penguin response to habitat limits of all ice or no ice. Then we considered results of statistical modeling at the temporal interannual-decadal scale in regard to penguin response over a continuum of rather complex, meso- to large-scale habitat conditions, some of which have opposing and others interacting effects. The ENSEMBLE meso/decadal-scale output projects a marked narrowing of penguins' zoogeographic range at the 2°C point. Colonies north of 70° S are projected to decrease or disappear: 50% of Emperor colonies (40% of breeding population) and 75% of Adélie colonies (70% of breeding population), but limited growth might occur south of 73° S. Net change would result largely from positive responses to increase in polynya persistence at high latitudes, overcome by decreases in pack ice cover at lower latitudes and, particularly for Emperors, ice thickness. Adélie Penguins might colonize new breeding habitat where concentrated pack ice diverges and/or disintegrating ice shelves expose coastline. Limiting increase will be decreased persistence of pack ice north of the Antarctic Circle, as this species requires daylight in its wintering areas. Adélies would be affected negatively by increasing snowfall, predicted to increase in certain areas owing to intrusions of warm, moist marine air due to changes in the Polar Jet Stream.This project was funded by the World Wildlife Fund and the
National Science Foundation, NSF grant OPP-0440643 (D. G.
Ainley), and a Marie-Curie Fellowship to S. Jenouvrier
ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas
<b>Objective</b>
<i>ABCB1</i> encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).<p></p>
<b>Methods</b>
The best candidates from fine-mapping analysis of 21 <i>ABCB1</i> SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.<p></p>
<b>Result</b>
Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, <i>ABCB1</i> expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.<p></p>
<b>Conclusion</b>
Our study represents the largest analysis of <i>ABCB1</i> SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.<p></p>
The Hominin Sites and Paleolakes Drilling Project:High-Resolution Paleoclimate Records from the East African Rift System and Their Implications for Understanding the Environmental Context of Hominin Evolution
The possibility of a causal relationship between Earth history processes and hominin evolution in Africa has been the subject of intensive paleoanthropological research for the last 25 years. One fundamental question is: can any geohistorical processes, in particular, climatic ones, be characterized with sufficient precision to enable temporal correlation with events in hominin evolution and provide support for a possible causal mechanism for evolutionary changes? Previous attempts to link paleoclimate and hominin evolution have centered on evidence from the outcrops where the hominin fossils are found, as understanding whether and how hominin populations responded to habitat change must be examined at the local basinal scale. However, these outcrop records typically provide incomplete, low-resolution climate and environmental histories, and surface weathering often precludes the application of highly sensitive, state-of-the-art paleoenvironmental methods. Continuous and well-preserved deep-sea drill core records have provided an alternative approach to reconstructing the context of hominin evolution, but have been collected at great distances from hominin sites and typically integrate information over vast spatial scales. The goal of the Hominin Sites and Paleolakes Drilling Project (HSPDP) is to analyze climate and other Earth system dynamics using detailed paleoenvironmental data acquired through scientific drilling of lacustrine depocenters at or near six key paleoanthropological sites in Kenya and Ethiopia. This review provides an overview of a unique collaboration of paleoanthropologists and earth scientists who have joined together to explicitly explore key hypotheses linking environmental history and mammalian (including hominin) evolution and potentially develop new testable hypotheses. With a focus on continuous, high-resolution proxies at timescales relevant to both biological and cultural evolution, the HSPDP aims to dramatically expand our understanding of the environmental history of eastern Africa during a significant portion of the Late Neogene and Quaternary, and to generate useful models of long-term environmental dynamics in the regionpublishersversionPeer reviewe
Measuring Winds From Space to Reduce the Uncertainty in the Southern Ocean Carbon Fluxes: Science Requirements and Proposed Mission
Strong winds in Southern Ocean storms drive air-sea carbon and heat fluxes. These fluxes are integral to the global climate system and the wind speeds that drive them are increasing. The current scatterometer constellation measuring vector winds remotely undersamples these storms and the higher winds within them, leading to potentially large biases in Southern Ocean wind reanalyses and the fluxes that derive from them. This observing system design study addresses these issues in two ways. First, we describe an addition to the scatterometer constellation, called Southern Ocean Storms -- Zephyr, to increase the frequency of independent observations, better constraining high winds. Second, we show that potential reanalysis wind biases over the Southern Ocean lead to uncertainty over the sign of the net winter carbon flux. More frequent independent observations per day will capture these higher winds and reduce the uncertainty in estimates of the global carbon and heat budgets
Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer.
Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first-line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7x10-5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression.This project has been supported by a grant from Cancer Australia. The Mayo Clinic GWAS was supported by R01CA114343 (Haplotype-based genome screen for ovarian cancer loci). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith. The AOCS was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, the National Health and Medical Research Council (NHMRC) of Australia (grants 400281, 400413), Cancer Council Victoria, Cancer Council Queensland, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, and Cancer Council Tasmania. G. Chenevix-Trench is a Senior Principal Research fellow of the NHMRC. Y. Lu is funded by NHMRC grant 496675, S. MacGregor is supported by an NHMRC career development award, S. Edwards and J. French are supported by Fellowships from the National Breast Cancer Foundation (NBCF) Australia. The QIMR Berghofer groups were supported by NHMRC project grants (1051698 to SM and 1058415 to SLE and JDF) and a Weekend to End Women’s Cancer Research Grant (to SLE). A deFazio is funded by the University of Sydney Cancer Research Fund and A deFazio and PR Harnett are funded by the Cancer Institute NSW through the Sydney-West Translational Cancer Research Centre. B. Gao is supported by NHMRC and Cancer Institute NSW scholarship. KBM and MO’R are funded by CR-UK. The Bavarian study (BAV) was supported by ELAN Funds of the University of Erlangen-Nuremberg. HSK would like to thank Ira Schwaab for her tireless work on sample preparation. The Belgian study (BEL) was funded by Nationaal Kankerplan and we would like to thank Gilian Peuteman, Thomas Van Brussel and Dominiek Smeets for technical assistance. The Japanese study (JPN) was funded by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare. The International
Collaborative Ovarian Neoplasm study (ICON)7 trial team would like to
thank the Medical Research Council (MRC) Clinical Trial Unit (CTU) at the
University of London (UCL), the ICON7 Translational Research Sub-group,
and the University of Leeds for their work on the coordination of samples
and data from the ICON7 trial. The LAX study (Women’s Cancer Program) was supported by the American Cancer Society Early Detection Professorship (120950-SIOP-06-258-06-COUN) and Entertainment Industry Foundation. Funding for MALOVA (MAL) was provided by research grant RO1 CA 61107 from the National Cancer Institute, Bethesda, MD; research grant 94 222 52 from the Danish Cancer Society, Copenhagen, Denmark; and the Mermaid I project. The Mayo Clinic study (MAYO) was supported by R01 CA122443, P50 CA136393. The Oregon study (ORE) was funded by the Sherie Hildreth Ovarian Cancer Research Fund and the OHSU Foundation. We would like to thank all members of Scottish Gynaecological Clinical Trials group and the SCOTROC1 investigators. SCOTROC1 (SRO) was funded by Cancer Research UK, and the SCOTROC biological studies were supported by Cancer Research UK (grant C536/A6689). RSH receives support from NIH/NIGMS grant K08GM089941, NIH/NCI grant R21 CA139278, NIH/NIGMS grant UO1GM61393, University of Chicago Cancer Center Support Grant (#P30 CA14599) and Breast Cancer SPORE Career Development Award.This is the final version of the article. It first appeared from Impact Journals via http://dx.doi.org/10.18632/oncotarget.704
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe