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1.
  • 2017
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  • 2021
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3.
  • Glasbey, JC, et al. (author)
  • 2021
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7.
  • Snodgrass, C., et al. (author)
  • The 67P/Churyumov-Gerasimenko observation campaign in support of the Rosetta mission
  • 2017
  • In: Philosophical Transactions. Series A. - : The Royal Society. - 1364-503X .- 1471-2962. ; 375:2097
  • Journal article (peer-reviewed)abstract
    • We present a summary of the campaign of remote observations that supported the European Space Agency's Rosetta mission. Telescopes across the globe (and in space) followed comet 67P/ Churyumov-Gerasimenko from before Rosetta's arrival until nearly the end of the mission in September 2016. These provided essential data for mission planning, large-scale context information for the coma and tails beyond the spacecraft and a way to directly compare 67P with other comets. The observations revealed 67P to be a relatively 'well-behaved' comet, typical of Jupiter family comets and with activity patterns that repeat from orbit to orbit. Comparison between this large collection of telescopic observations and the in situ results from Rosetta will allow us to better understand comet coma chemistry and structure. This work is just beginning as the mission ends-in this paper, we present a summary of the ground-based observations and early results, and point to many questions that will be addressed in future studies. This article is part of the themed issue 'Cometary science after Rosetta'.
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9.
  • Neale, R. E., et al. (author)
  • Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2020
  • 2021
  • In: Photochemical & Photobiological Sciences. - : Springer Science and Business Media LLC. - 1474-905X .- 1474-9092. ; 20, s. 1-67
  • Journal article (peer-reviewed)abstract
    • This assessment by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) provides the latest scientific update since our most recent comprehensive assessment (Photochemical and Photobiological Sciences, 2019, 18, 595-828). The interactive effects between the stratospheric ozone layer, solar ultraviolet (UV) radiation, and climate change are presented within the framework of the Montreal Protocol and the United Nations Sustainable Development Goals. We address how these global environmental changes affect the atmosphere and air quality; human health; terrestrial and aquatic ecosystems; biogeochemical cycles; and materials used in outdoor construction, solar energy technologies, and fabrics. In many cases, there is a growing influence from changes in seasonality and extreme events due to climate change. Additionally, we assess the transmission and environmental effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, in the context of linkages with solar UV radiation and the Montreal Protocol.
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10.
  • Machiela, Mitchell J., et al. (author)
  • Characterization of Large Structural Genetic Mosaicism in Human Autosomes
  • 2015
  • In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
  • Journal article (peer-reviewed)abstract
    • Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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11.
  • Wang, Zhaoming, et al. (author)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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12.
  • Jacobs, Kevin B, et al. (author)
  • Detectable clonal mosaicism and its relationship to aging and cancer.
  • 2012
  • In: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
  • Journal article (peer-reviewed)abstract
    • In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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13.
  • Machiela, Mitchell J, et al. (author)
  • Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
  • 2016
  • In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
  • Journal article (peer-reviewed)abstract
    • To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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  • Bartels-Rausch, T., et al. (author)
  • A review of air-ice chemical and physical interactions (AICI): Liquids, quasi-liquids, and solids in snow
  • 2014
  • In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:3, s. 1587-1633
  • Journal article (peer-reviewed)abstract
    • Snow in the environment acts as a host to rich chemistry and provides a matrix for physical exchange of contaminants within the ecosystem. The goal of this review is to summarise the current state of knowledge of physical processes and chemical reactivity in surface snow with relevance to polar regions. It focuses on a description of impurities in distinct compartments present in surface snow, such as snow crystals, grain boundaries, crystal surfaces, and liquid parts. It emphasises the microscopic description of the ice surface and its link with the environment. Distinct differences between the disordered air-ice interface, often termed quasi-liquid layer, and a liquid phase are highlighted. The reactivity in these different compartments of surface snow is discussed using many experimental studies, simulations, and selected snow models from the molecular to the macro-scale. Although new experimental techniques have extended our knowledge of the surface properties of ice and their impact on some single reactions and processes, others occurring on, at or within snow grains remain unquantified. The presence of liquid or liquid-like compartments either due to the formation of brine or disorder at surfaces of snow crystals below the freezing point may strongly modify reaction rates. Therefore, future experiments should include a detailed characterisation of the surface properties of the ice matrices. A further point that remains largely unresolved is the distribution of impurities between the different domains of the condensed phase inside the snowpack, i.e. in the bulk solid, in liquid at the surface or trapped in confined pockets within or between grains, or at the surface. While surface-sensitive laboratory techniques may in the future help to resolve this point for equilibrium conditions, additional uncertainty for the environmental snowpack may be caused by the highly dynamic nature of the snowpack due to the fast metamorphism occurring under certain environmental conditions. Due to these gaps in knowledge the first snow chemistry models have attempted to reproduce certain processes like the long-term incorporation of volatile compounds in snow and firn or the release of reactive species from the snowpack. Although so far none of the models offers a coupled approach of physical and chemical processes or a detailed representation of the different compartments, they have successfully been used to reproduce some field experiments. A fully coupled snow chemistry and physics model remains to be developed. © Author(s) 2014.
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15.
  • Steffen, Will, et al. (author)
  • Stratigraphic and Earth System approaches to defining the Anthropocene
  • 2016
  • In: Earth's Future. - 2328-4277. ; 4:8, s. 324-345
  • Research review (peer-reviewed)abstract
    • Stratigraphy provides insights into the evolution and dynamics of the Earth System over its long history. With recent developments in Earth System science, changes in Earth System dynamics can now be observed directly and projected into the near future. An integration of the two approaches provides powerful insights into the nature and significance of contemporary changes to Earth. From both perspectives, the Earth has been pushed out of the Holocene Epoch by human activities, with the mid-20th century a strong candidate for the start date of the Anthropocene, the proposed new epoch in Earth history. Here we explore two contrasting scenarios for the future of the Anthropocene, recognizing that the Earth System has already undergone a substantial transition away from the Holocene state. A rapid shift of societies toward the UN Sustainable Development Goals could stabilize the Earth System in a state with more intense interglacial conditions than in the late Quaternary climate regime and with little further biospheric change. In contrast, a continuation of the present Anthropocene trajectory of growing human pressures will likely lead to biotic impoverishment and a much warmer climate with a significant loss of polar ice.
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  • Gasperini, C., et al. (author)
  • Prolonged-release fampridine treatment improved subject-reported impact of multiple sclerosis: Item-level analysis of the MSIS-29
  • 2016
  • In: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X. ; 370, s. 123-131
  • Journal article (peer-reviewed)abstract
    • Prolonged-release (PR) fampridine is approved to treat walking impairment in persons with multiple sclerosis (MS); however, treatment benefits may extend beyond walking. MOBILE was a phase 2, 24-week, double-blind, placebo-controlled exploratory study to assess the impact of 10mg PR-fampridine twice daily versus placebo on several subject-assessed measures. This analysis evaluated the physical and psychological health outcomes of subjects with progressing or relapsing MS from individual items of the Multiple Sclerosis Impact Scale (MSIS-29). PR-fampridine treatment (n=68) resulted in greater improvements from baseline in the MSIS-29 physical (PHYS) and psychological (PSYCH) impact subscales, with differences of 89% and 148% in mean score reduction from baseline (n=64) at week 24 versus placebo, respectively. MSIS-29 item analysis showed that a higher percentage of PR-fampridine subjects had mean improvements in 16/20 PHYS and 6/9 PSYCH items versus placebo after 24weeks. Post hoc analysis of the 12-item Multiple Sclerosis Walking Scale (MSWS-12) improver population (≥8-point mean improvement) demonstrated differences in mean reductions from baseline of 97% and 111% in PR-fampridine MSIS-29 PHYS and PSYCH subscales versus the overall placebo group over 24weeks. A higher percentage of MSWS-12 improvers treated with PR-fampridine showed mean improvements in 20/20 PHYS and 8/9 PSYCH items versus placebo at 24weeks. In conclusion, PR-fampridine resulted in physical and psychological benefits versus placebo, sustained over 24weeks. © 2016 The Authors
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  • Ghavami, Saeid, et al. (author)
  • S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3
  • 2010
  • In: Cell Research. - : Springer Science and Business Media LLC. - 1001-0602 .- 1748-7838. ; 20:3, s. 314-331
  • Journal article (peer-reviewed)abstract
    • The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity in various cells of different origins. Here, we present evidence that the underlying molecular mechanisms involve both programmed cell death I (PCD I, apoptosis) and PCD II (autophagy)-like death. Treatment of cells with S100A8/A9 caused the increase of Beclin-1 expression as well as Atg12-Atg5 formation. S100A8/A9-induced cell death was partially inhibited by the specific PI3-kinase class III inhibitor, 3-methyladenine (3-MA), and by the vacuole H+-ATPase inhibitor, bafilomycin-A1 (Baf-A1). S100A8/A9 provoked the translocation of BNIP3, a BH3 only pro-apoptotic Bcl2 family member, to mitochondria. Consistent with this finding, ΔTM-BNIP3 overexpression partially inhibited S100A8/A9-induced cell death, decreased reactive oxygen species (ROS) generation, and partially protected against the decrease in mitochondrial transmembrane potential in S100A8/A9-treated cells. In addition, either ΔTM-BNIP3 overexpression or N-acetyl-L-cysteine co-treatment decreased lysosomal activation in cells treated with S100A8/A9. Our data indicate that S100A8/A9-promoted cell death occurs through the cross-talk of mitochondria and lysosomes via ROS and the process involves BNIP3.
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  • Head, Martin J., et al. (author)
  • The Great Acceleration is real and provides a quantitative basis for the proposed Anthropocene Series/Epoch
  • 2022
  • In: Episodes. - : International Union of Geological Sciences. - 0705-3797 .- 2586-1298. ; 45:4, s. 359-376
  • Journal article (peer-reviewed)abstract
    • The Anthropocene was conceptualized in 2000 to reflect the extensive impact of human activities on our planet, and subsequent detailed analyses have revealed a substantial Earth System response to these impacts beginning in the mid-20th century. Key to this understanding was the discovery of a sharp upturn in a multitude of global socio-economic indicators and Earth System trends at that time; a phenomenon termed the ‘Great Acceleration’. It coincides with massive increases in global human-consumed energy and shows the Earth System now on a trajectory far exceeding the earlier variability of the Holocene Epoch, and in some respects the entire Quaternary Period. The evaluation of geological signals similarly shows the mid-20th century as representing the most appropriate inception for the Anthropocene. A recent mathematical analysis has nonetheless challenged the significance of the original Great Acceleration data. We examine this analytical approach and reiterate the robustness of the original data in supporting the Great Acceleration, while emphasizing that intervals of rapid growth are inevitably time-limited, as recognised at the outset. Moreover, the exceptional magnitude of this growth remains undeniable, reaffirming the centrality of the Great Acceleration in justifying a formal chronostratigraphic Anthropocene at the rank of series/epoch.
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  • Hüpers, Andre, et al. (author)
  • Release of mineral-bound water prior to subduction tied to shallow seismogenic slip off Sumatra
  • 2017
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 356:6340, s. 841-844
  • Journal article (peer-reviewed)abstract
    • Plate-boundary fault rupture during the 2004 Sumatra-Andaman subduction earthquake extended closer to the trench than expected, increasing earthquake and tsunami size. International Ocean Discovery Program Expedition 362 sampled incoming sediments offshore northern Sumatra, revealing recent release of fresh water within the deep sediments. Thermal modeling links this freshening to amorphous silica dehydration driven by rapid burial-induced temperature increases in the past 9 million years. Complete dehydration of silicates is expected before plate subduction, contrasting with prevailing models for subduction seismogenesis calling for fluid production during subduction. Shallow slip offshore Sumatra appears driven by diagenetic strengthening of deeply buried fault-forming sediments, contrasting with weakening proposed for the shallow Tohoku-Oki 2011 rupture, but our results are applicable to other thickly sedimented subduction zones including those with limited earthquake records.
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21.
  • McNeill, Lisa C., et al. (author)
  • Understanding Himalayan erosion and the significance of the Nicobar Fan
  • 2017
  • In: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 475, s. 134-142
  • Journal article (peer-reviewed)abstract
    • A holistic view of the Bengal-Nicobar Fan system requires sampling the full sedimentary section of the Nicobar Fan, which was achieved for the first time by International Ocean Discovery Program (IODP) Expedition 362 west of North Sumatra. We identified a distinct rise in sediment accumulation rate (SAR) beginning similar to 9.5 Ma and reaching 250-350 m/Myr in the 9.5-2 Ma interval, which equal or far exceed rates on the Bengal Fan at similar latitudes. This marked rise in SAR and a constant Himalayan-derived provenance necessitates a major restructuring of sediment routing in the Bengal-Nicobar submarine fan. This coincides with the inversion of the Eastern Himalayan Shillong Plateau and encroachment of the west-propagating Indo-Burmese wedge, which reduced continental accommodation space and increased sediment supply directly to the fan. Our results challenge a commonly held view that changes in sediment flux seen in the Bengal-Nicobar submarine fan were caused by discrete tectonic or climatic events acting on the Himalayan-Tibetan Plateau. Instead, an interplay of tectonic and climatic processes caused the fan system to develop by punctuated changes rather than gradual progradation.
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22.
  • R. Hinojosa, Diego, et al. (author)
  • Solubilizing Benzodifuranone-Based Conjugated Copolymers with Single-Oxygen-Containing Branched Side Chains
  • 2024
  • In: ACS Applied Polymer Materials. - 2637-6105. ; 6:1, s. 457-465
  • Journal article (peer-reviewed)abstract
    • Single-oxygen-containing branched side chains are designed and used to solubilize n-type copolymers consisting of BDF (benzodifuranone), isatin, and thiophene-based units. We present a simple synthetic approach to side chains with varying linker distances between the backbone and the branching point. The synthetic pathway is straightforward and modular and starts with commercially available reagents. The side chains give rise to excellent solubilities of BDF-thiophene copolymers of up to 90 mg/mL, while still being moderate in size (26-34 atoms large). The excellent solubility furthermore allows high molar mass materials. BDF-thiophene copolymers are characterized in terms of optoelectronic and thermoelectric properties. The electrical conductivity of chemically doped polymers is found to scale with molar mass, reaching ∼1 S/cm for the highest molar mass and longest backbone-branching point distance.
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  • Schweinsberg, Martin, et al. (author)
  • Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
  • 2021
  • In: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
  • Journal article (peer-reviewed)abstract
    • In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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  • Digby, Janet E, et al. (author)
  • Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin.
  • 2010
  • In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 209:1, s. 89-95
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: A major site of action for the atheroprotective drug nicotinic acid (NA) is adipose tissue, via the G-protein-coupled receptor, GPR109A. Since, adipose tissue is an active secretory organ that contributes both positively and negatively to systemic inflammatory processes associated with cardiovascular disease, we hypothesized that NA would act directly upon adipocytes to alter the expression of pro-inflammatory chemokines, and the anti-inflammatory adipokine adiponectin.METHODS AND RESULTS: TNF-alpha treatment (1.0ng/mL) of 3T3-L1 adipocytes resulted in an increase in gene expression of fractalkine (9+/-3.3-fold, P<0.01); monocyte chemoattractant protein-1 (MCP-1) (24+/-1.2-fold, P<0.001), 'regulated upon activation, normal T cell expressed and secreted' (RANTES) (500+/-55-fold, P<0.001) and inducible nitric oxide synthase (iNOS) (200+/-70-fold, P<0.05). The addition of NA (10(-4)M) to TNF-alpha-treated adipocytes attenuated expression of fractalkine (50+/-12%, P<0.01); MCP-1 (50+/-6%, P<0.01), RANTES (70+/-3%, P<0.01) and iNOS (60+/-16%). This pattern was mirrored in protein released from the adipocytes into the surrounding media. The effect on gene expression was neutralised by pre-treatment with pertussis toxin. NA attenuated macrophage chemotaxis (by 27+/-3.5%, P<0.001) towards adipocyte conditioned media. By contrast, NA, (10(-6)-10(-3)M) increased, in a dose-dependent manner, mRNA of the atheroprotective hormone adiponectin (3-5-fold n=6, P<0.01).CONCLUSIONS: NA suppresses pro-atherogenic chemokines and upregulates the atheroprotective adiponectin through a G-protein-coupled pathway. Since adipose tissue has the potential to contribute to both systemic and local (perivascular) inflammation associated with atherosclerosis our results suggest a new "pleiotropic" role for NA.
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