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Sökning: WFRF:(Hansell P)

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1.
  • Davies, G., et al. (författare)
  • Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
  • 2018
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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  • Wain, Louise V, et al. (författare)
  • Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
  • 2017
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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  • Lønborg, C., et al. (författare)
  • A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)
  • 2024
  • Ingår i: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 16:2, s. 1107-1119
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) concentrations are used to characterize the dissolved organic matter (DOM) pool and are important components ofbiogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOMv1; available at https://doi.org/10.1594/PANGAEA.964012, Lønborg et al., 2023) compiling previously published and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complementedby hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables(e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon andtotal alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However,most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the SouthernHemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC,20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequenceDOC > DON > DOP, reflecting both differences in the maturity of the analytical methods and the greater focuson carbon cycling by the aquatic science community. The global database shows that the average DOC concentration in coastal waters (average ± standard deviation (SD): 182±314 µmolC L−1; median: 103 µmolC L−1) is13-fold higher than the average coastal DON concentration (13.6 ± 30.4 µmol N L−1; median: 8.0 µmol N L−1),which is itself 39-fold higher than the average coastal DOP concentration (0.34 ± 1.11 µmol P L−1; median:0.18 µmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and willhelp facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochemical processes; closing nutrient budgets; estimating carbon, nitrogen, and phosphorous pools; and establishing abaseline for modelling future changes in coastal waters. 
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  • Savage, J. E., et al. (författare)
  • Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:7, s. 912-919
  • Tidskriftsartikel (refereegranskat)abstract
    • Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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  • Charette, M. A., et al. (författare)
  • The Transpolar Drift as a Source of Riverine and Shelf-Derived Trace Elements to the Central Arctic Ocean
  • 2020
  • Ingår i: Journal of Geophysical Research-Oceans. - : American Geophysical Union (AGU). - 2169-9275 .- 2169-9291. ; 125:5
  • Tidskriftsartikel (refereegranskat)abstract
    • A major surface circulation feature of the Arctic Ocean is the Transpolar Drift (TPD), a current that transports river-influenced shelf water from the Laptev and East Siberian Seas toward the center of the basin and Fram Strait. In 2015, the international GEOTRACES program included a high-resolution pan-Arctic survey of carbon, nutrients, and a suite of trace elements and isotopes (TEIs). The cruises bisected the TPD at two locations in the central basin, which were defined by maxima in meteoric water and dissolved organic carbon concentrations that spanned 600 km horizontally and similar to 25-50 m vertically. Dissolved TEIs such as Fe, Co, Ni, Cu, Hg, Nd, and Th, which are generally particle-reactive but can be complexed by organic matter, were observed at concentrations much higher than expected for the open ocean setting. Other trace element concentrations such as Al, V, Ga, and Pb were lower than expected due to scavenging over the productive East Siberian and Laptev shelf seas. Using a combination of radionuclide tracers and ice drift modeling, the transport rate for the core of the TPD was estimated at 0.9 +/- 0.4 Sv (10(6) m(3)s(-1)). This rate was used to derive the mass flux for TEIs that were enriched in the TPD, revealing the importance of lateral transport in supplying materials beneath the ice to the central Arctic Ocean and potentially to the North Atlantic Ocean via Fram Strait. Continued intensification of the Arctic hydrologic cycle and permafrost degradation will likely lead to an increase in the flux of TEIs into the Arctic Ocean. Plain Language Summary A major feature of the Arctic Ocean circulation is the Transpolar Drift (TPD), a surface current that carries ice and continental shelf-derived materials from Siberia across the North Pole to the North Atlantic Ocean. In 2015, an international team of oceanographers conducted a survey of trace elements in the Arctic Ocean, traversing the TPD. Near the North Pole, they observed much higher concentrations of trace elements in surface waters than in regions on either side of the current. These trace elements originated from land, and their journey across the Arctic Ocean is made possible by chemical reactions with dissolved organic matter that originates mainly in Arctic rivers. This study reveals the importance of rivers and shelf processes combined with strong ocean currents in supplying trace elements to the central Arctic Ocean and onward to the Atlantic. These trace element inputs are expected to increase as a result of permafrost thawing and increased river runoff in the Arctic, which is warming at a rate much faster than anywhere else on Earth. Since many of the trace elements are essential building blocks for ocean life, these processes could lead to significant changes in the marine ecosystems and fisheries of the Arctic Ocean.
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  • Charette, M, et al. (författare)
  • The Transpolar Drift as a Source of Riverine and Shelf‐Derived Trace Elements to the Central Arctic Ocean
  • 2020
  • Ingår i: Journal of Geophysical Research - Oceans. - 2169-9275 .- 2169-9291. ; 125, s. 1-34
  • Tidskriftsartikel (refereegranskat)abstract
    • A major surface circulation feature of the Arctic Ocean is the Transpolar Drift (TPD), a current that transports river‐influenced shelf water from the Laptev and East Siberian Seas toward the center of the basin and Fram Strait. In 2015, the international GEOTRACES program included a high‐resolution pan‐Arctic survey of carbon, nutrients, and a suite of trace elements and isotopes (TEIs). The cruises bisected the TPD at two locations in the central basin, which were defined by maxima in meteoric water and dissolved organic carbon concentrations that spanned 600 km horizontally and ~25–50 m vertically. Dissolved TEIs such as Fe, Co, Ni, Cu, Hg, Nd, and Th, which are generally particle‐reactive but can be complexed by organic matter, were observed at concentrations much higher than expected for the openocean setting. Other trace element concentrations such as Al, V, Ga, and Pb were lower than expected due to scavenging over the productive East Siberian and Laptev shelf seas. Using a combination of radionuclide tracers and ice drift modeling, the transport rate for the core of the TPD was estimated at 0.9 ± 0.4 Sv(106m3 s−1). This rate was used to derive the mass flux for TEIs that were enriched in the TPD, revealing the importance of lateral transport in supplying materials beneath the ice to the central Arctic Ocean and potentially to the North Atlantic Ocean via Fram Strait. Continued intensification of the Arctic hydrologicc ycle and permafrost degradation will likely lead to an increase in the flux of TEIs into the Arctic Ocean.
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  • Satizabal, Claudia L., et al. (författare)
  • Genetic architecture of subcortical brain structures in 38,851 individuals
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
  • Tidskriftsartikel (refereegranskat)abstract
    • Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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  • Shrine, Nick, et al. (författare)
  • New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
  • 2019
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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  • Hibar, Derrek P., et al. (författare)
  • Novel genetic loci associated with hippocampal volume
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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  • Artigas, MS, et al. (författare)
  • Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation
  • 2015
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 8658-
  • Tidskriftsartikel (refereegranskat)abstract
    • Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
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  • Daşu, Alexandru, et al. (författare)
  • The relationship between vascular oxygen distribution and tissue oxygenation
  • 2009
  • Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 645, s. 255-260
  • Tidskriftsartikel (refereegranskat)abstract
    • Tumour oxygenation could be investigated through several methods that use various measuring principles and can therefore highlight its different aspects. The results have to be subsequently correlated, but this might not be straightforward due to intrinsic limitations of the measurement methods. This study describes an analysis of the relationship between vascular and tissue oxygenations that may help the interpretation of results. Simulations have been performed with a mathematical model that calculates the tissue oxygenation for complex vascular arrangements by taking into consideration the oxygen diffusion into the tissue and its consumption at the cells. The results showed that while vascular and tissue oxygenations are deterministically related, the relationship between them is not unequivocal and this could lead to uncertainties when attempting to correlate them. However, theoretical simulation could bridge the gap between the results obtained with various methods.
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  • Toma-Dasu, Iuliana, et al. (författare)
  • Quantifying tumour hypoxia by PET imaging : a theoretical analysis
  • 2009
  • Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 645, s. 267-272
  • Tidskriftsartikel (refereegranskat)abstract
    • Information on tumour oxygenation could be obtained from various imaging methods, but the success of incorporating it into treatment planning depends on the accuracy of quantifying it. This study presents a theoretical analysis of the efficiency of measuring tumour hypoxia by PET imaging. Tissue oxygenations were calculated for ranges of biologically relevant physiological parameters and were then used to simulate PET images for markers with different uptake characteristics. The resulting images were used to calculate dose distributions that could lead to predefined tumour control levels. The results have shown that quantification of tumour hypoxia with PET may lead to different values according to the tracer used and the tumour site investigated. This would in turn be reflected into the dose distributions recommended by the optimisation algorithms. However, irrespective of marker-specific differences, focusing the radiation dose to the hypoxic areas appears to reduce the average tumour dose needed to achieve a certain control level.
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  • Do, Lan, et al. (författare)
  • High Sensitivity Method to Estimate Distribution of Hyaluronan Molecular Sizes in Small Biological Samples Using Gas-Phase Electrophoretic Mobility Molecular Analysis.
  • 2015
  • Ingår i: International Journal of Cell Biology. - : Hindawi Limited. - 1687-8876 .- 1687-8884.
  • Tidskriftsartikel (refereegranskat)abstract
    • Hyaluronan is a negatively charged polydisperse polysaccharide where both its size and tissue concentration play an important role in many physiological and pathological processes. The various functions of hyaluronan depend on its molecular size. Up to now, it has been difficult to study the role of hyaluronan in diseases with pathological changes in the extracellular matrix where availability is low or tissue samples are small. Difficulty to obtain large enough biopsies from human diseased tissue or tissue from animal models has also restricted the study of hyaluronan. In this paper, we demonstrate that gas-phase electrophoretic molecular mobility analyzer (GEMMA) can be used to estimate the distribution of hyaluronan molecular sizes in biological samples with a limited amount of hyaluronan. The low detection level of the GEMMA method allows for estimation of hyaluronan molecular sizes from different parts of small organs. Hence, the GEMMA method opens opportunity to attain a profile over the distribution of hyaluronan molecular sizes and estimate changes caused by disease or experimental conditions that has not been possible to obtain before.
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  • Friederich-Persson, M., et al. (författare)
  • Kidney Hypoxia, Attributable to Increased Oxygen Consumption, Induces Nephropathy Independently of Hyperglycemia and Oxidative Stress
  • 2013
  • Ingår i: Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0194-911X .- 1524-4563. ; 62:5, s. 914-919
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetic nephropathy is strongly associated with both increased oxidative stress and kidney tissue hypoxia. The increased oxidative stress causes increased kidney oxygen consumption resulting in kidney tissue hypoxia. To date, it has been difficult to determine the role of kidney hypoxia, per se, for the development of nephropathy. We tested the hypothesis that kidney hypoxia, without confounding factors such as hyperglycemia or elevated oxidative stress, results in nephropathy. To induce kidney hypoxia, dinitrophenol (30 mg per day per kg bodyweight by gavage), a mitochondrial uncoupler that increases oxygen consumption and causes kidney hypoxia, was administered for 30 consecutive days to rats. Thereafter, glomerular filtration rate, renal blood flow, kidney oxygen consumption, kidney oxygen tension, kidney concentrations of glucose and glycogen, markers of oxidative stress, urinary protein excretion, and histological findings were determined and compared with vehicle-treated controls. Dinitrophenol did not affect arterial blood pressure, renal blood flow, glomerular filtration rate, blood glucose, or markers of oxidative stress but increased kidney oxygen consumption, and reduced cortical and medullary concentrations of glucose and glycogen, and resulted in intrarenal tissue hypoxia. Furthermore, dinitrophenol treatment increased urinary protein excretion, kidney vimentin expression, and infiltration of inflammatory cells. In conclusion, increased mitochondrial oxygen consumption results in kidney hypoxia and subsequent nephropathy. Importantly, these results demonstrate that kidney tissue hypoxia, per se, without confounding hyperglycemia or oxidative stress, may be sufficient to initiate the development of nephropathy and therefore demonstrate a new interventional target for treating kidney disease.
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  • Liss, Per, et al. (författare)
  • Renal failure in 57 925 patients undergoing coronary procedures using iso-osmolar or low-osmolar contrast media
  • 2006
  • Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 70:10, s. 1811-1817
  • Tidskriftsartikel (refereegranskat)abstract
    • We compared the Swedish Coronary Angiography and Angioplasty Registry with the Swedish 'Hospital Discharge Register' to assess contrast media (CM)-induced renal failure. Hospitals used only one type CM. From 2000 to 2003, iodixanol (iso-osmolar) was used in 45 485 patients, ioxaglate (low osmolar) in 12 440 subjects. To include the earlier used CM iohexol (low osmolar), analysis extended back to 1990 (86 334 patients). Incidence of clinically significant renal failure was greatest for patients receiving the iso-osmolar CM iodixanol (1.7%). Ioxaglate-treated patients had a significantly lower renal failure incidence (0.8%, P<0.001). The odds ratio for iodixanol-treated patients was significantly higher than for ioxaglate (1 vs 0.48, P<0.001). In subsets of either diabetic patients or patients with previous renal failure, odds ratios for renal failure remained greater in the iodixanol groups (P<0.01). Hospitals switching CM to iodixanol experienced a doubling in clinically significant renal failure after cardiac procedures. Dialysis was required in 0.2% of patients receiving iodixanol, which was significantly higher (P<0.01) than for ioxaglate-treated patients (0.1%). Iohexol-treated patients had a similar low risk for developing clinically significant renal failure (0.9%) as ioxaglate. In conclusion, risk of developing renal failure and required dialysis after coronary procedures is higher when patients received iodixanol than ioxaglate or iohexol.
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  • Nagata, Toshi, et al. (författare)
  • Emerging concepts on microbial processes in the bathypelagic ocean – ecology, biogeochemistry and genomics
  • 2010
  • Ingår i: Deep-sea research. Part II, Topical studies in oceanography. - : Elsevier BV. - 0967-0645 .- 1879-0100. ; 57:16, s. 1519-1536
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper synthesizes recent findings regarding microbial distributions and processes in the bathypelagic ocean (depth > 1000 m). Abundance, production and respiration of prokaryotes reflect supplies of particulate and dissolved organic matter to the bathypelagic zone. Better resolution of carbon fluxes mediated by deep microbes requires further testing on the validity of conversion factors. Archaea, especially marine Crenarchaeota Group I, are abundant in deep waters where they can fix dissolved inorganic carbon. Viruses appear to be important in the microbial loop in deep waters, displaying remarkably high virus to prokaryote abundance ratios in some oceanic regions. Sequencing of 18S rRNA genes revealed a tremendous diversity of small-sized protists in bathypelagic waters. Abundances of heterotrophic nanoflagellates (HNF) and ciliates decrease with depth more steeply than prokaryotes; nonetheless, data indicated that HNF consumed half of prokaryote production in the bathypelagic zone. Aggregates are important habitats for deep-water microbes, which produce more extracellular enzymes (on a per-cell basis) than surface communities. The theory of marine gel formation provides a framework to unravel complex interactions between microbes and organic polymers. Recent data on the effects of hydrostatic pressure on microbial activities indicate that bathypelagic microbial activity is generally higher under in situ pressure conditions than at atmospheric pressures. High-throughput sequencing of 16S rRNA genes revealed a remarkable diversity of Bacteria in the bathypelagic ocean. Metagenomics and comparative genomics of piezophiles reveal not only the high diversity of deep sea microbes but also specific functional attributes of these piezophilic microbes, interpreted as an adaptation to the deep water environment. Taken together, the data compiled on bathypelagic microbes indicate that, despite high-pressure and low-temperature conditions, microbes in the bathypelagic ocean dynamically interact with complex mixtures of organic matter, responding to changes in the ocean's biogeochemical state.
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  • Nygren, A, et al. (författare)
  • Red-cell trapping in the rat renal microcirculation induced by low-osmolar contrast media and mannitol
  • 1993
  • Ingår i: Investigative Radiology. - 0020-9996 .- 1536-0210. ; 28:11, s. 1033-1038
  • Tidskriftsartikel (refereegranskat)abstract
    • RATIONALE AND OBJECTIVES: In acute renal failure after ischemia, intravascular obstruction by trapped red blood cells in the microvasculature of the renal outer medulla is a consistent finding. The influence of intravenously injected contrast media (CM) on such obstruction was investigated. METHODS: Anesthetized rats were subjected to 45 minutes of unilateral renal ischemia. Red-cell trapping in ischemically injured kidneys and in the contralateral uninjured kidneys was estimated from the intrarenal distribution of 51Cr-labelled erythrocytes after injection of ioxaglate or iopamidol in a dose of 1,600 mg I/kg body weight. As an osmolar control substance, mannitol (950 mOsm/kg) was given to a third group and isotonic Ringer's solution was administered to a fourth group. RESULTS: In the uninjured kidneys, treatment with ioxaglate or mannitol resulted in no red-cell trapping, while the iopamidol-treated group showed red-cell trapping in the inner stripe of the outer medulla in a dose-dependent manner. In the ischemically injured kidneys, both CM and mannitol enhanced the red-cell trapping in the inner stripe of the renal medulla. CONCLUSION: The results indicate that intravenously administered ioxaglate and iopamidol enhance the microvascular obstructions evoked by ischemic injury and that iopamidol may induce local impairment in renal medullary microcirculation in a normal kidney.
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