| 1. |
- Alexandersson, Bjarki T., et al.
(author)
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Diverticulosis is not associated with altered gut microbiota nor is it predictive of future diverticulitis : a population-based colonoscopy study
- 2023
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:10, s. 1131-1138
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Journal article (peer-reviewed)abstract
- Background: The etiopathogenesis of diverticular disease is unknown.Objective: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study.Methods: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/−5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not.Results: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not (p = .027).Conclusions: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas. The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.
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| 2. |
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| 3. |
- Aldi, Silvia, et al.
(author)
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Dual roles of heparanase in human carotid plaque calcification
- 2019
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In: Atherosclerosis. - : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 283, s. 127-136
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Journal article (peer-reviewed)abstract
- Background and aims: Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-beta-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification. Previously, we reported upregulation of HPSE in human carotid endarterectomies from symptomatic patients and showed correlation of HPSE expression with markers of inflammation and increased thrombogenicity. The present aim is to investigate HPSE expression in relation to genes associated with osteogenesis and osteolysis and the effect of elevated HPSE expression on calcification and osteolysis in vitro.Methods: Transcriptomic and immunohistochemical analyses were performed using the Biobank of Karolinska Endarterectomies (BiKE). In vitro calcification and osteolysis were analysed in human carotid smooth muscle cells overexpressing HPSE and bone marrow-derived osteoclasts from HPSE-transgenic mice respectively.Results: HPSE expression correlated primarily with genes coupled to osteoclast differentiation and function in human carotid atheromas. HPSE was expressed in osteoclast-like cells in atherosclerotic lesions, and HPSE-transgenic bone marrow-derived osteoclasts displayed a higher osteolytic activity compared to wild-type cells. Contrarily, human carotid SMCs with an elevated HPSE expression demonstrated markedly increased mineralization upon osteogenic differentiation.Conclusions: We suggest that HPSE may have dual functions in vascular calcification, depending on the stage of the disease and presence of inflammatory cells. While HPSE plausibly enhances mineralization and osteogenic differentiation of vascular smooth muscle cells, it is associated with inflammation-induced osteoclast differentiation and activity in advanced atherosclerotic plaques.
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| 4. |
- Baron, Tomasz, et al.
(author)
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Test-retest reliability of new and conventional echocardiographic parameters of left ventricular systolic function
- 2019
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In: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 108:4, s. 355-365
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Journal article (peer-reviewed)abstract
- Background: Reliability of left ventricular function measurements depends on actual biological conditions, repeated registrations and their analyses.Objective: To investigate test–retest reliability of speckle-tracking-derived strain measurements and its determinants compared to the conventional parameters, such as ejection fraction (EF), LV volumes and mitral annular plane systolic excursion (MAPSE).Methods: In 30 patients with a wide range of left ventricular function (mean EF 46.4 ± 16.4%, range 14–73%), standard echo views were acquired independently in a blinded fashion by two different echocardiographers in immediate sequence and analyzed off-line by two independent readers, creating 4 data sets per patient. Test–retest reliability of studied parameters was calculated using the smallest detectable change (SDC) and a total, inter-acquisition and inter-reader intra-class correlation coefficient (ICC).Results: The smallest detectable change normalized to the mean absolute value of the measured parameter (SDCrel) was lowest for MAPSE (10.7%). SDCrel for EF was similar to GLS (14.2 and 14.7%, respectively), while SDCrel for CS was much higher (35.6%). The intra-class correlation coefficient was excellent (> 0.9) for all measures of the left ventricular function. Intra-patient inter-acquisition reliability (ICCacq) was significantly better than inter-reader reliability (ICCread) (0.984 vs. 0.950, p = 0.03) only for EF, while no significant difference was observed for any other LV function parameter. Mean intra-subject standard deviations were significantly correlated to the mean values for CS and LV volumes, but not for the other studied parameters.Conclusions: In a test–retest setting, both with normal and impaired left ventricular function, the smallest relative detectable change of EF, GLS and MAPSE was similar (11–15%), but was much higher for CS (35%). Surprisingly, reliability of GLS was not superior to that of EF. Acquisition and reader to a similar extent influenced the reliability of measurements of all left ventricular function measures except for ejection fraction, where the reliability was more dependent on the reader than on the acquisition.
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| 5. |
- Buckler, Andrew J., et al.
(author)
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Virtual Transcriptomics Noninvasive Phenotyping of Atherosclerosis by Decoding Plaque Biology From Computed Tomography Angiography Imaging
- 2021
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In: Arteriosclerosis, Thrombosis and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 41:5, s. 1738-1750
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Journal article (peer-reviewed)abstract
- Objective: Therapeutic advancements in atherosclerotic cardiovascular disease have improved prevention of ischemic stroke and myocardial infarction, but diagnostic methods for atherosclerotic plaque phenotyping to aid individualized therapy are lacking. In this feasibility study, we aimed to elucidate plaque biology by decoding the molecular phenotype of plaques through analysis of computed-tomography angiography images, making a predictive model for plaque biology referred to as virtual transcriptomics. Approach and Results: We employed machine intelligence using paired computed-tomography angiography and transcriptomics from carotid endarterectomies of 40 patients undergoing stroke-preventive surgery for carotid stenosis. Computed tomography angiographies were analyzed with novel software for accurate characterization of plaque morphology and plaque transcriptomes obtained from microarrays, followed by mathematical modeling for prediction of molecular signatures. Four hundred fourteen coding and noncoding RNAs were robustly predicted using supervised models to estimate gene expression based on plaque morphology. Examples of predicted transcripts included ion transporters, cytokine receptors, and a number of microRNAs whereas pathway analyses demonstrated enrichment of several biological processes relevant for the pathophysiology of atherosclerosis and plaque instability. Finally, the ability of the models to predict plaque gene expression was demonstrated using computed tomography angiographies from 4 sequestered patients and comparisons with transcriptomes of corresponding lesions. Conclusions: The results of this pilot study show that atherosclerotic plaque phenotyping by image analysis of conventional computed-tomography angiography can elucidate the molecular signature of atherosclerotic lesions in a multiscale setting. The study holds promise for optimized personalized therapy in the prevention of myocardial infarction and ischemic stroke, which warrants further investigations in larger cohorts.
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| 6. |
- Church, Tamara L., et al.
(author)
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A microporous polymer based on nonconjugated hindered biphenyls that emits blue light
- 2024
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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Journal article (peer-reviewed)abstract
- Microporous organic polymers that have three-dimensional connectivity stemming from monomers with tetrahedral or tetrahedron-like geometry can have high surface areas and strong fluorescence. There are however few examples of such polymers based on hindered biaryls, and their fluorescence has not been studied. Hypothesizing that the contortion in a hindered biphenyl moiety would modulate the optical properties of a polymer built from it, we synthesized a meta-enchained polyphenylene from a 2,2',6,6'-tetramethylbiphenyl-based monomer, in which the two phenyl rings are nearly mutually perpendicular. The polymer was microporous with S-BET = 495 m(2) g(-1). The polymer absorbed near-UV light and emitted blue fluorescence despite the meta-enchainment that would have been expected to break the conjugation. A related copolymer, synthesized from 2,2',6,6'-tetramethylbiphenyl-based and unsubstituted biphenyl-based monomers, was microporous but not fluorescent.
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| 7. |
- Fredriksson, Tobias, et al.
(author)
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Diagnostic patterns of serum inflammatory protein markers in children with Lyme neuroborreliosis
- 2024
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In: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 15:4
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Journal article (peer-reviewed)abstract
- Definite diagnosis of Lyme neuroborreliosis (LNB) requires investigation of serum and cerebrospinal fluid (CSF). Thus, lumbar puncture is necessary, and requires administration of sedating drugs in children. This study aimed to investigate if a pattern of different inflammatory biomarkers in serum could contribute to the selection of children for lumbar puncture in suspected LNB. Patients were included from a cohort of children who was previously investigated for LNB including serum and CSF sampling during the years 2010-2014. The multiplex proximity extension assay (PEA) inflammation panel Target 96 (Olink Bioscience, Uppsala, Sweden) was used to examine 92 biomarkers in serum. Based on the presence of CSF pleocytosis and Borrelia-specific antibodies, patients were divided into a definite LNB group (n=61) and a non-LNB control group (n=58). Following PEA and statistical analysis with multivariate logistic regression, five biomarkers remained significant (p < 0.001), which were included in a calculation of protein index. The index biomarkers were CST5, IL-15RA, CXCL10, DNER and CX3CL1. A receiver operating characteristic curve was constructed from the index, which showed an 80 % sensitivity and 81 % specificity. Area under the curve was 0.889. We offer evidence that, with further refinements, patterns of serum biomarkers might help identify those children more or less likely to have LNB, perhaps ultimately decreasing the need for lumbar punctures.
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| 8. |
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| 9. |
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| 10. |
- Holmlund, Anders, et al.
(author)
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Porphyromonas gingivalis (Pg) a possible link between impaired oral health and acute myocardial infarction
- 2011
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 148:2, s. 148-153
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Journal article (peer-reviewed)abstract
- Objective: To investigate if oral health parameters were impaired in patients with myocardial infarction (MI) and if there was an association with serum antibody levels against the periodontal pathogens Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa). Methods: A case-control study consisting of 100 patients with MI and 100 age- and sex-matched controls from the same geographic area was investigated regarding oral health. Results: The MI group had significantly more periodontal bone loss (PBL), number of deepened pockets (NDP), and bleeding on probing (BOP), and lower number of teeth (NT) than the controls. After adjustment for known cardiovascular risk factors NT, BOP, and NDP still remained significantly related to MI (p = 0.014, p = 0.02, and p = 0.0069, respectively). IgG antibody levels against Pg were higher in subjects with MI (p = 0.043), as well as in those with > 4 deepened pockets (p = 0.05), BOP > 20% (p = 0.001) and PBL (p = 0.0003). However, indicating a causal pathway, the relationship between MI and Pg IgG disappeared when the oral parameters were included in the logistic regression model (p = 0.69). No correlation was seen between MI and Aa in the present study. Conclusion: Patients with MI had an impaired oral health compared to controls. Furthermore, IgG levels against Pg were related to both MI and oral health, suggesting this pathogen as a possible link between oral health and CVD.
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| 11. |
- Jensen, Jette Nygaard, et al.
(author)
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Comparison of antibiotic prescribing and antimicrobial resistance in urinary tract infections at the municipal level among women in two Nordic regions
- 2018
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In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 73:8, s. 2207-2214
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Journal article (peer-reviewed)abstract
- Objectives: To describe and compare the prescribing of antibiotics used for urinary tract infections and its correlation with resistance in Escherichia coli in urinary samples across two adjacent regions - the Capital Region and the Skaane Region - and their municipalities in Denmark and Sweden. Methods: The Capital Region consists of 29 municipalities and 725 960 female inhabitants aged ≥18 years and the Skaane Region consists of 33 municipalities and 515 668 female inhabitants aged ≥18 years. Aggregated data from outpatient care on the prescribing of pivmecillinam, trimethoprim and nitrofurantoin from both regions were analysed. The Department of Clinical Microbiology in both regions provided data on E. coli resistance in urinary samples from women aged ≥18 years. Data were measured as the number of prescriptions/1000 women/year, number of DDDs/1000 women/year and DDDs/prescription. Correlation analyses between antibiotic prescribing and antibiotic resistance rates were performed. Results: Antibiotic prescribing and resistance rates were significantly higher in the Capital Region compared with the Skaane Region. Large variations in prescription and resistance rates were found at the municipal level, but there were no correlations between the antibiotic prescription and resistance rates when each region was analysed separately. Conclusions: Although closely related, there are large differences in antibiotic prescribing and antibiotic resistance. It is suggested that the regional guidelines are an important driver and explanatory factor for the variations; however, further research is needed in this new field and factors such as the influence of cultural aspects should be the target of further research.
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| 12. |
- Karlöf, Eva, et al.
(author)
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Correlation of computed tomography with carotid plaque transcriptomes associates calcification with lesion-stabilization
- 2019
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In: Atherosclerosis. - Stockholm : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 288, s. 175-185
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Journal article (peer-reviewed)abstract
- Background and aims: Unstable carotid atherosclerosis causes stroke, but methods to identify patients and lesions at risk are lacking. We recently found enrichment of genes associated with calcification in carotid plaques from asymptomatic patients. Here, we hypothesized that calcification represents a stabilising feature of plaques and investigated how macro-calcification, as estimated by computed tomography (CT), correlates with gene expression profiles in lesions. Methods: Plaque calcification was measured in pre-operative CT angiographies. Plaques were sorted into high- and low-calcified, profiled with microarrays, followed by bioinformatic analyses. Immunohistochemistry and qPCR were performed to evaluate the findings in plaques and arteries with medial calcification from chronic kidney disease patients. Results: Smooth muscle cell (SMC) markers were upregulated in high-calcified plaques and calcified plaques from symptomatic patients, whereas macrophage markers were downregulated. The most enriched processes in high-calcified plaques were related to SMCs and extracellular matrix (ECM) organization, while inflammation, lipid transport and chemokine signaling were repressed. These findings were confirmed in arteries with high medial calcification. Proteoglycan 4 (PRG4) was identified as the most upregulated gene in association with plaque calcification and found in the ECM, SMA+ and CD68+/TRAP + cells. Conclusions: Macro-calcification in carotid lesions correlated with a transcriptional profile typical for stable plaques, with altered SMC phenotype and ECM composition and repressed inflammation. PRG4, previously not described in atherosclerosis, was enriched in the calcified ECM and localized to activated macrophages and smooth muscle-like cells. This study strengthens the notion that assessment of calcification may aid evaluation of plaque phenotype and stroke risk.
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| 13. |
- Perri, Saverio, et al.
(author)
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Socio-political feedback on the path to net zero
- 2023
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In: One Earth. - 2590-3330 .- 2590-3322. ; 6:6, s. 725-737
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Journal article (peer-reviewed)abstract
- Anthropogenic CO2 emissions must soon approach net zero to stabilize the global mean temperature. Although several international agreements have advocated for coordinated climate actions, their implementation has remained below expectations. One of the main challenges of international cooperation is different degrees of socio-political acceptance of decarbonization. Here, we interrogate a minimalistic model of the coupled human-natural system representing the impact of such socio-political acceptance on investments in clean energy infrastructure and the path to net-zero emissions. Despite its simplicity, the model can reproduce complex interactions between human and natural systems, and it can disentangle the effects climate policies from those of socio-political acceptance on the path to net zero. Although perfect coordination remains unlikely, because clean energy investments are limited by myopic economic strategies and policy systems that promote free-riding, more realistic decentralized cooperation with partial efforts from each actor could still lead to significant cuts in emissions.
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| 14. |
- Skogman, Barbro Hedin, 1967-, et al.
(author)
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Cytokines and chemokines in cerebrospinal fluid in relation to diagnosis, clinical presentation and recovery in children being evaluated for Lyme neuroborreliosis
- 2020
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In: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 11:3
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Journal article (peer-reviewed)abstract
- In Lyme neuroborrelios (LNB), the immune response has been in focus, but the association between different cytokines/chemokines and clinical manifestations in LNB patients has not been fully investigated. The aim of this study was to evaluate a large number of cytokines and chemokines in cerebrospinal fluid (CSF) in relation to diagnosis, clinical presentation and recovery in children being evaluated for LNB.Materials and methods: Pediatric patients (n = 105) were recruited at seven Swedish pediatric departments during 2010-14. Serum and CSF samples were drawn on admission, before start of antibiotic treatment. Patients diagnosed as Definite LNB or Possible LNB were categorized as LNBtot patients, all LNBtot patients presented with pleocytosis in CSF. Patients diagnosed as Non-LNB or Other diagnosis were categorized as Controls(tot), all controls(tot) presented without pleocytosis in CSF. Multiplex bead array (Luminex) kits were used for analyses of 41 different cytokines/chemokines in CSF (Millipore).Results: Twenty-eight cytokines/chemokines were detectable in CSF and the levels of 26 of these mediators were significantly higher in LNBtot patients than in Controls(tot). In a discriminant analysis, a combination of four cytokines/chemokines (CXCL1, GM-CSF, IL-7 and IL-10) were shown to independently separate relevant patient groups. Furthermore, an IL-10/CXCL1 ratio was created and shown to have an improved diagnostic performance in distinguishing LNBtot vs Non-LNB patients, as compared to CXCL13 in CSF. No immune mediator differed significantly, when comparing LNBtot patients with different clinical presentation on admission or when comparing patients with or without recovery within 2 months of admission.Conclusion: A discriminant analysis was shown to be useful to distinguish the independently most important cytokines/chemokines (CXCL1, GM-CSF, IL-7 and IL-10) in CSF, in order to discriminate LNBtot patients from Non-LNB patients. An IL-10/CXCL1 ratio was shown to have a promising diagnostic profile with a better performance than the chemokine CXCL13 in CSF. However, further evaluation is required to address future possible usefulness of these cytokines and chemokines in laboratory diagnostics in LNB, including control groups with neuro-inflammation. No significant associations were found between CSF immune mediator levels and clinical presentation or recovery in pediatric LNB patients.
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| 15. |
- Soranno, Patricia A., et al.
(author)
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LAGOS-NE : A multi-scaled geospatial and temporal database of lake ecological context and water quality for thousands of U.S. lakes
- 2017
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In: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 6:12, s. 1-22
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Journal article (peer-reviewed)abstract
- Understanding the factors that affect water quality and the ecological services provided by freshwater ecosystems is an urgent global environmental issue. Predicting how water quality will respond to global changes not only requires water quality data, but also information about the ecological context of individual water bodies across broad spatial extents. Because lake water quality is usually sampled in limited geographic regions, often for limited time periods, assessing the environmental controls of water quality requires compilation of many data sets across broad regions and across time into an integrated database. LAGOS-NE accomplishes this goal for lakes in the northeastern-most 17 US states. LAGOS-NE contains data for 51101 lakes and reservoirs larger than 4 ha in 17 lake-rich US states. The database includes 3 datamodules for: lake location and physical characteristics for all lakes; ecological context (i.e., the land use, geologic, climatic, and hydrologic setting of lakes) for all lakes; and in situmeasurements of lake water quality for a subset of the lakes fromthe past 3 decades for approximately 2600–12 000 lakes depending on the variable. The database contains approximately 150000 measures of total phosphorus, 200 000 measures of chlorophyll, and 900 000 measures of Secchi depth. The water quality data were compiled from87 lake water quality data sets fromfederal, state, tribal, and non-profit agencies, university researchers, and citizen scientists. This database is one of the largest andmost comprehensive databases of its type because it includes both in situmeasurements and ecological context data. Because ecological context can be used to study a variety of other questions about lakes, streams, and wetlands, this database can also be used as the foundation for other studies of freshwaters at broad spatial and ecological scales
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| 16. |
- Söderström, Leif, et al.
(author)
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Increased carotid artery lesion inflammation upon treatment with the CD137 agonistic antibody 2A
- 2017
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In: Circulation Journal. - 1346-9843. ; 81:12, s. 1945-1952
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Journal article (peer-reviewed)abstract
- Background: Increased inflammatory activity destabilizes the atherosclerotic lesion and may lead to atherothrombosis and symptomatic cardiovascular disease. Co-stimulatory molecules, such as CD137, are key regulators of inflammation, and CD137 activity regulates inflammation in experimental atherosclerosis. Here, we hypothesized that CD137 activation promotes carotid artery inflammation and atherothrombosis. Methods and Results: In a model of inducible atherothrombosis with surgical ligation of the right carotid artery and a subsequent placement of a polyethene cuff, elevated levels of CD137 and CD137 ligand mRNA in atherothrombotic vs. non-atherothrombotic murine carotid lesions was observed. Mice treated with the CD137 agonistic antibody 2A showed signs of increased inflammation in the aorta and a higher proportion of CD8+ T cells in spleen and blood. In carotid lesions of 2A-treated mice, significantly higher counts of CD8+ and major histocompatibility (MHC)-class II molecule I-Ab+ cells were observed. Treatment with the CD137 agonistic antibody 2A did not significantly affect the atherothrombosis frequency in 16-week-old mice in this model. Conclusions: Levels of CD137 and CD137 ligand mRNA were higher in advanced atherosclerotic disease compared to control vessels, and treatment with the CD137 agonistic antibody 2A, in a murine model for inducible atherothrombosis promoted vascular inflammation, but had no significant effect on atherothrombosis frequency at this early disease stage.
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| 17. |
- Åström, Maria, et al.
(author)
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Habitat preferences and conservation of the Marbled Jewel Beetle Poecilonota variolosa (Buprestidae)
- 2013
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In: Journal of Insect Conservation. - : Springer Science and Business Media LLC. - 1366-638X .- 1572-9753. ; 17:6, s. 1145-1154
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Journal article (peer-reviewed)abstract
- Detailed knowledge on habitat requirements is a key to successful conservation actions. The marbled jewel beetle Poecilonota variolosa (Buprestidae) has a wide global distribution but populations are often scarce and typically fragmented. In Sweden it is monophagous on aspen Populus tremula and is classified as near threatened on the Swedish Red List due to its rapid population decline. This study aimed to investigate habitat preferences and regional-scale distribution patterns of P. variolosa in southern Sweden in order to suggest conservation measures. Aspen trees in four study areas in the province of Småland were surveyed for exit holes during late summer 2011. The occurrence and number of exit holes (both new and old ones) per tree were compared between study areas and habitat types, and were related to the sun exposure and bark thickness of individual trees. Further, the occurrence of new and older exit holes was related to tree sun exposure and bark thickness. The most preferred habitat types were aspens on clear-cuts, followed by roadside aspens, aspens in pastures, and aspens in closed forest. Thick bark and high sun exposure were consistently significant as predictors for both occurrence and number of new exit holes per tree. The majority of exit holes were located towards south. Our results indicate several useful management measures: to retain aspen on clear-cuts, to cut alongside roads and around some selected coarse aspens in closed forests and in pastures.
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