| 1. |
- Forchhammer, Mads C., et al.
(författare)
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Zackenberg in a circumpolar context
- 2008
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Ingår i: Advances in Ecological Research. - 0065-2504. ; 40, s. 499-544
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Throughout the Northern Hemisphere, changes in local and regional climate conditions are coupled to the recurring and persistent large-scale patterns of pressure and circulation anomalies spanning vast geographical areas, the so-called teleconnection patterns. Indeed, the atmospheric fluctuations described by the North Atlantic Oscillation (NAO) are closely associated with the last four decades of inter-annual variability in local snow and ice conditions observed in the Arctic. Since the NAO has also been connected with changes in the global climate, the behaviour of species, communities and other ecosystem elements at Zackenberg in relation to the NAO enables us to view these in circumpolar and global contexts. Large-scale systems like the NAO constitute the link between the global change and local climate variability to which ecosystem components respond. Here, we place selected ecosystem elements from the monitoring programme Zackenberg Basic presented in previous chapters in a circumpolar context related to NAO-mediated climatic changes. We begin by linking the local variability in winter weather conditions at Zackenberg to fluctuations in the NAO. We then proceed by linking the observed intra- and inter-annual behaviour of selected ecosystem elements to changes in the NAO. The functional ecosystem characteristics in focus are landscape gas exchange dynamics phenological patterns at different trophic levels, consumer-resource dynamics and community stability. The influence of the NAO is presented and discussed in a broader perspective based on information obtained from other arctic localities. The relation between the NAO and the Zackenberg winter weather, is nonlinear, reflecting differential effects of the NAO as the index moves between high and low phases. The inverse hyperbolic relationship found between the NAO and the amount of winter snow was also evident as non-linear response in organisms and systems to inter-annual changes in the NAO. Responses investigated included growth and reproduction in plants and animals, population dynamics and synchrony, inter-trophic interactions and community stability together with system feedback dynamics.
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| 2. |
- Meltofte, Hans, et al.
(författare)
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Introduction
- 2008
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Ingår i: High-arctic ecosystem dynamics in a changing climate - Ten years of monitoring and research at Zackenberg Research Station, Northeast Greenland (Advances in Ecological Research). - 0065-2504. - 9780123736659 ; 40, s. 1-12
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Our continuously changing global environment requires continuous and detailed monitoring for us to understand how ecosystems are structured and function in response to climatic changes. Understanding the arctic ecosystems is of particular importance (Oechel et al., 1997). Indeed, rather than in boreal and temperate regions, the forecasted climatic changes will be first and most pronounced in the Arctic. Hence, performing long-term monitoring of an arctic ecosystem provides us with the unique ability to not only give "early warnings" of climate change impacts but also, and perhaps even more important, predict how and where in the ecosystem these will be most pronounced and with what consequences for stability, structure and function. Since 1995, Zackenberg Ecological Research Operations (ZERO) has monitored annually over 1500 variables concurrently across the physical and biological compartments of a single high-arctic terrestrial ecosystem in central Northeast Greenland. This makes ZERO the most integrated and comprehensive long-term monitoring and research programme presently operating in the Arctic. This book explores the complex physical and ecological long-term dynamics of a high-arctic terrestrial ecosystem. Since the book is based on data from ZERO, this introductory chapter presents the structural and organisational foundation for ZERO. Following our introduction are four chapters providing the climatic and ecological background together with a presentation of the study area. The rest of the book is devoted entirely to the physical, ecological and ecosystem processes.
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| 3. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 4. |
- Elberling, Bo, et al.
(författare)
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High Arctic soil CO2 and CH4 production controlled by temperature, water, freezing and snow
- 2008
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Ingår i: High-arctic ecosystem dynamics in a changing climate - Ten years of monitoring and research at Zackenberg Research Station, Northeast Greenland (Advances in Ecological Research). - 0065-2504. - 9780123736659 ; 40, s. 441-472
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Soil gas production processes, mainly anaerobic or aerobic soil respiration, drive major gas fluxes across the soil-atmosphere interface. Carbon dioxide (CO2) effluxes, an efflux which in most ecosystems is a result of both autotrophic and heterotrophic respiration, in particular have received international attention. The importance of both CO2 and methane (CH4) fluxes are emphasised in the Arctic because of the large amount of soil organic carbon stored in terrestrial ecosystems and changes in uptake and release due to climate changes. This chapter focuses on controls on spatial and temporal trends in subsurface CO2 and CH4 production as well as on transport and release of gases from the soil observed in the valley Zackenbergdalen. A dominance of near-surface temperatures controlling both spatial and seasonal trends is shown based on data obtained using closed chamber and eddy-correlation techniques as well as in manipulated field plots and in controlled incubation experiments. Despite variable temperature sensitivities reported, most data can be fairly well fitted to exponential temperature-dependent equations. The water content (at wet sites linked to the depth to the water table) is a second major factor regulating soil respiration processes, but the effect is quite different in contrasting vegetation types. Dry heath sites are shown to be periodically water limited during the growing season and respond therefore with high respiration rates when watered. In contrast, water saturated conditions during most of the growing season in the fen areas hinder the availability of oxygen, resulting in both CO2 and CH4 production. Thus, water table drawdown results in decreasing CH4 effluxes but increasing CO2 effluxes. Additional controls on gas production are shown to be related to the availability of substrate and plant productivity. Subsurface gas production will produce partial and total pressure gradient causing gas transport, which in well-drained soils is mainly controlled by diffusion, whereas gas advection, bubbles and transport through roots and stems may be important in more saturated soils. Bursts of CO2 gas have been observed during spring thaw and confirmed in controlled soil thawing experiments. Field observations as well as experimental work suggest that such bursts represent partly on-going soil respiration and a physical release of gas produced during the winter. The importance of winter soil respiration is emphasised because of the fact that microbial respiration in Zackenberg samples is noted down to a least -18 degrees C. Hence, the importance of winter respiration and burst events in relation to seasonal and future climate trends requires more than just summer measurements. For example, the autumn period seems important as snowfall prior to low air temperature may insulate the soil, keeping soil temperatures high. This will extend the period of high soil respiration rates and thereby increase the importance of the winter period for the annual carbon balance. Because of the complexity of factors controlling subsurface gas production, we conclude that different parts of the landscape will respond quite differently to the same climate changes as well as that short-term effects are likely to be different from long-term effects.
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| 5. |
- Elberling, Bo, et al.
(författare)
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Soil and Plant Community Characteristics and Dynamics at Zackenberg
- 2008
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Ingår i: High-arctic ecosystem dynamics in a changing climate - Ten years of monitoring and research at Zackenberg Research Station, Northeast Greenland (Advances in Ecological Research). - 0065-2504. - 9780123736659 ; 40, s. 223-248
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Arctic soils hold large amounts of nutrients in the weatherable minerals and the soil organic matter, which slowly decompose. The decomposition processes release nutrients to the plant-available nutrient pool as well as greenhouse gases to the atmosphere. Changes in climatic conditions, for example, changes in the distribution of snow, water balance and the length of the growing season, are likely to affect the complex interactions between plants, abiotic and biotic soil processes as well as the composition of soil micro- and macro-fauna and thereby the overall decomposition rates. These interactions, in turn, will influence soil-plant functioning and vegetation composition in the short as well as in the long term. In this chapter, we report on soils and. plant communities and their distribution patterns in the valley Zackenbergdalen and focus on the detailed investigations within five dominating plant communities. These five communities are located along an ecological gradient in the landscape and are closely related to differences in water availability. They are therefore indirectly formed as a result of the distribution of landforms, redistribution of snow and drainage conditions. Each of the plant communities is closely related to specific nutrient levels and degree of soil development including soil element accumulation and translocation, for example, organic carbon. Results presented here show that different parts of the landscape have responded quite differently to the same overall climate changes the last 10 years and thus, most likely in the future too. Fens represent the wettest sites holding large reactive buried carbon stocks. A warmer climate will cause a permafrost degradation, which most likely will result in anoxic decomposition and increasing methane emissions. However, the net gas emissions at fen sites are sensitive to long-term changes in the water table level. Indeed, increasing maximum active layer depth at fen sites has been recorded together with a decreasing water level at Zackenberg. This is in line with the first signs of increasing extension of grasslands at the expense of fens. In contrast, the most exposed and dry areas have less soil carbon, and decomposition processes are periodically water limited. Here, an increase in air temperatures may increase active layer depth more than at fen sites, but water availability will be critical in determining nutrient cycling and plant production. Field manipulation experiments of increasing temperature, water supply and nutrient addition show that soil-plant interactions are sensitive to these variables. However, additional plant-specific investigations are needed before net effects of climate changes on different landscape and plant communities can be integrated in a landscape context and used to assess the net ecosystem effect of future climate scenarios.
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| 6. |
- Grøndahl, Louise, et al.
(författare)
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Spatial and interannual variability of trace gas fluxes in a heterogeneous High Arctic landscape
- 2008
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Ingår i: High-arctic ecosystem dynamics in a changing climate - Ten years of monitoring and research at Zackenberg Research Station, Northeast Greenland (Advances in Ecological Research). - 0065-2504. - 9780123736659 ; 40, s. 473-498
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Summertime measurements of CO2 and CH4 fluxes were carried out over a range of high-arctic ecosystem types in the valley Zackenbergdalen since 1996 using both chamber and eddy covariance methodology. The net ecosystem CO2 exchange and CH4 flux data presented reveal a high degree of inter-annual variability within the dominant vegetation types in the valley, but also show distinct differences between them. In particular, the wet and dry parts of the valley show distinct differences. In general, the wet parts of the valley, the fens dominated by white cotton grass Eriophorum scheuchzeri, show high productivity, also in comparison with other sites, whereas CO2 uptake rates in the white arctic bell heather Cassiope tetragona and mountain avens Dryas spp.-dominated heaths are much smaller. Also within the different ecosystem types, a high degree of spatial variability can be documented. The spatial variability both within and between ecosystem types is especially pronounced for the CH4 flux and can, at least partly, be related to differences in vegetation composition and water table level. The importance of the CH4 emission from the various ecosystem types is evaluated both in relation to carbon and greenhouse gas budgets. In both wet and drier ecosystem components, inter-annual variability seems best explained through differences in the amount and distribution of snow in spring and the length of the growing season. A large number of replicate chamber measurements carried out over various vegetation types in the valley are used to produce a synthesis of 10 years of flux data available on growing season carbon dynamics and CH4 emission patterns in the individual parts of this high-arctic ecosystem and relates the differences between the ecosystems found in Zackenbergdalen to comparable sites in the circumpolar North.
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| 7. |
- Habermeyer, Michael, et al.
(författare)
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Anthocyanidins modulate the activity of human DNA topoisomerases I and II and affect cellular DNA integrity.
- 2005
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Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 18:9, s. 1395-404
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we investigated the effect of anthocyanidins on human topoisomerases I and II and its relevance for DNA integrity within human cells. Anthocyanidins bearing vicinal hydroxy groups at the B-ring (delphinidin, DEL; cyanidin, CY) were found to potently inhibit the catalytic activity of human topoisomerases I and II, without discriminating between the IIalpha and the IIbeta isoforms. However, in contrast to topoisomerase poisons, DEL and CY did not stabilize the covalent DNA-topoisomerase intermediates (cleavable complex) of topoisomerase I or II. Using recombinant topoisomerase I, the presence of CY or DEL (> or = 1 microM) effectively prohibited the stabilization of the cleavable complex by the topoisomerase I poison camptothecin. We furthermore investigated whether the potential protective effect vs topoisomerase I poisons is reflected also on the cellular level, affecting the DNA damaging properties of camptothecin. Indeed, in HT29 cells, low micromolar concentrations of DEL (1-10 microM) significantly diminished the DNA strand breaking effect of camptothecin (100 microM). However, at concentrations > or = 50 microM, all anthocyanidins tested (delphinidin, cyanidin, malvidin, pelargonidin, and paeonidin), including those not interfering with topoisomerases, were found to induce DNA strand breaks in the comet assay. All of these analogues were able to compete with ethidium bromide for the intercalation into calf thymus DNA and to replace the minor groove binder Hoechst 33258. These data indicate substantial affinity to double-stranded DNA, which might contribute at least to the DNA strand breaking effect of anthocyanidins at higher concentrations (> or = 50 microM).
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| 8. |
- Jelenkovic, Aline, et al.
(författare)
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Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
- 2015
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
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Tidskriftsartikel (refereegranskat)abstract
- A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
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| 9. |
- Margaryan, Ashot, et al.
(författare)
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Population genomics of the Viking world
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 585:7825, s. 390-396
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Tidskriftsartikel (refereegranskat)abstract
- The maritime expansion of Scandinavian populations during the Viking Age (about ad 750–1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci—including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response—in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.
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| 10. |
- Mirza, Mansoor Raza, et al.
(författare)
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A phase I study of the PARP inhibitor niraparib in combination with bevacizumab in platinum-sensitive epithelial ovarian cancer: NSGO AVANOVA1/ENGOT-OV24
- 2019
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Ingår i: Cancer Chemotherapy and Pharmacology. - : SPRINGER. - 0344-5704 .- 1432-0843. ; 84:4, s. 791-798
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Tidskriftsartikel (refereegranskat)abstract
- Background Combining poly(ADP-ribose) polymerase (PARP) inhibitors with antiangiogenic agents appeared to enhance activity vs PARP inhibitors alone in a randomized phase II trial. Materials and methods In AVANOVA (NCT02354131) part 1, patients with measurable/evaluable high-grade serous/endometrioid platinum-sensitive ovarian cancer received bevacizumab 15 mg/kg every 21 days with escalating doses of niraparib capsules (100, 200, or 300 mg daily) in a 3 + 3 dose-escalation design. Primary objectives were to evaluate safety and tolerability and to determine the recommended phase II dose (RP2D). Results Three of 12 enrolled patients had germline BRCA2 mutations. In cycle 1, nine patients experienced grade 3 toxicities: five with hypertension, three with anemia, and one with thrombocytopenia. There was one dose-limiting toxicity (grade 4 thrombocytopenia with niraparib 300 mg), thus the RP2D was bevacizumab 15 mg/kg with niraparib 300 mg. The response rate was 50%; disease was stabilized in a further 42%. Median progression-free survival was 11.6 (95% confidence interval 8.4-20.1) months. Niraparib pharmacokinetics were consistent with historical single-agent data. Overlapping exposure was observed across the dose ranges tested on days 1 and 21. Conclusions There was one dose-limiting toxicity; other adverse events were typical PARP inhibitor and antiangiogenic class effects. Niraparib-bevacizumab showed promising activity; Part 2 (vs bevacizumab) was recently reported and phase III comparison with standard-of-care therapy is planned.
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