| 1. |
- Ebersole, Charles R., et al.
(författare)
-
Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
-
Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
-
Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
|
|
| 2. |
- Yi, Chuixiang, et al.
(författare)
-
Climate control of terrestrial carbon exchange across biomes and continents
- 2010
-
Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 5:3
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the relationships between climate and carbon exchange by terrestrial ecosystems is critical to predict future levels of atmospheric carbon dioxide because of the potential accelerating effects of positive climate-carbon cycle feedbacks. However, directly observed relationships between climate and terrestrial CO2 exchange with the atmosphere across biomes and continents are lacking. Here we present data describing the relationships between net ecosystem exchange of carbon (NEE) and climate factors as measured using the eddy covariance method at 125 unique sites in various ecosystems over six continents with a total of 559 site-years. We find that NEE observed at eddy covariance sites is (1) a strong function of mean annual temperature at mid-and high-latitudes, (2) a strong function of dryness at mid-and low-latitudes, and (3) a function of both temperature and dryness around the mid-latitudinal belt (45 degrees N). The sensitivity of NEE to mean annual temperature breaks down at similar to 16 degrees C (a threshold value of mean annual temperature), above which no further increase of CO2 uptake with temperature was observed and dryness influence overrules temperature influence.
|
|
| 3. |
- Hudson, Lawrence N, et al.
(författare)
-
The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
-
Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
-
Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
|
|
| 4. |
- Nicolas, Aude, et al.
(författare)
-
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
-
Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
-
Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
|
|
| 5. |
- Rodriguez-Espigares, Ismael, et al.
(författare)
-
GPCRmd uncovers the dynamics of the 3D-GPCRome
- 2020
-
Ingår i: Nature Methods. - : Springer Nature. - 1548-7091 .- 1548-7105. ; 17:8, s. 777-787
-
Tidskriftsartikel (refereegranskat)abstract
- G-protein-coupled receptors (GPCRs) are involved in numerous physiological processes and are the most frequent targets of approved drugs. The explosion in the number of new three-dimensional (3D) molecular structures of GPCRs (3D-GPCRome) over the last decade has greatly advanced the mechanistic understanding and drug design opportunities for this protein family. Molecular dynamics (MD) simulations have become a widely established technique for exploring the conformational landscape of proteins at an atomic level. However, the analysis and visualization of MD simulations require efficient storage resources and specialized software. Here we present GPCRmd (http://gpcrmd.org/), an online platform that incorporates web-based visualization capabilities as well as a comprehensive and user-friendly analysis toolbox that allows scientists from different disciplines to visualize, analyze and share GPCR MD data. GPCRmd originates from a community-driven effort to create an open, interactive and standardized database of GPCR MD simulations.
|
|
| 6. |
- Hagedorn, Gregor, et al.
(författare)
-
Concerns of young protesters are justified
- 2019
-
Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 364:6436, s. 139-140
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 7. |
- Hambäck, Peter, et al.
(författare)
-
Effects of body size, trophic mode and larval habitat on Diptera stoichiometry: a regional comparison
- 2009
-
Ingår i: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 118, s. 615-623
-
Tidskriftsartikel (refereegranskat)abstract
- Ecological stoichiometry has emerged as a tool for exploring nutrient demand and evolutionary responses to nutrient limitation. Previous studies of insects have found predictable variability in stoichiometry, both in relation to body size and trophic mode, at ordinal levels or higher. Our study further examines the evolutionary and ecological lability in these traits by comparing the effects of body size, trophic mode (larval and adult) and larval habitat on the stoichiometry of insects within one order (Diptera). The study also expands on previous work by analyzing trophic mode both at coarse (detritivore, herbivore, predator) and fine (high- vs low- nutrient quality resources within trophic categories) scales and by comparing nutrient stoichiometry in two geographical regions, Sweden and Arizona. As predicted, adults feeding on nectar or pollen had the lowest body N content in the dataset. Additionally, for Diptera with predatory larvae, species low N diets had lower body N content than those with high N diets. However, body N content was not consistently lower for all species with low N resources, as species feeding on plant material were indistinguishable in stoichiometry from predators with high N diets. We suggest that these results emerge because larval resource exploitation is poorly understood in herbivorous Diptera species. Body P content for Swedish Diptera decreased with body size for all trophic modes, and the only difference among trophic modes was that blood feeders had higher P content than other groups. The regional comparison further showed that the allometry of body P content is a labile trait that may vary at regional scales, as there was no allometric scaling of body P content in the Arizona data set, in contrast to the Swedish data set. These results are not easily explained by existing theoretical frameworks, but instead point to a general context-dependence of P stoichiometry, which should now be a focus for future work.
|
|
| 8. |
- Hudson, Lawrence N., et al.
(författare)
-
The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
-
Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
-
Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
|
|
| 9. |
- Kaiser, Vera B, et al.
(författare)
-
Homozygous loss-of-function variants in European cosmopolitan and isolate populations
- 2015
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:19, s. 5464-5475
-
Tidskriftsartikel (refereegranskat)abstract
- Homozygous Loss of Function (HLOF) variants provide a valuable window on gene function in humans, as well as an inventory of the human genes that are not essential for survival and reproduction. All humans carry at least a few HLOF variants, but the exact number of inactivated genes that can be tolerated is currently unknown - as are the phenotypic effects of losing function for most human genes. Here, we make use of 1,432 whole exome sequences from five European populations to expand the catalogue of known human HLOF mutations; after stringent filtering of variants in our dataset, we identify a total of 173 HLOF mutations, 76 (44%) of which have not been observed previously. We find that population isolates are particularly well suited to surveys of novel HLOF genes because individuals in such populations carry extensive runs of homozygosity, which we show are enriched for novel, rare HLOF variants. Further, we make use of extensive phenotypic data to show that most HLOFs, ascertained in population-based samples, appear to have little detectable effect on the phenotype. On the contrary, we document several genes directly implicated in disease that seem to tolerate HLOF variants. Overall HLOF genes are enriched for olfactory receptor function and are expressed in testes more often than expected, consistent with reduced purifying selection and incipient pseudogenisation.
|
|
| 10. |
- Kampen, Stefanie
(författare)
-
Structure-based Virtual Screening for Ligands of G Protein-coupled Receptors : Design of Allosteric and Dual-Target Modulators
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- G protein-coupled receptors (GPCRs) are integral membrane proteins responsible for signal transduction of extracellular stimuli into the cell. Because of their widespread distribution throughout the human body and important roles in physiological processes, GPCRs are prominent drug targets and approximately 34% of all approved drugs interact with members of this superfamily. GPCR ligands are used as drugs against various diseases, including neurodegenerative and neuropsychiatric disorders. The increased availability of GPCR structural information has enhanced understanding of GPCR function but also enables structure-based drug design (SBDD). This thesis focuses on SBDD targeting allosteric and orthosteric binding sites of GPCRs and strategies to identify multi-target ligands. Drug discovery campaigns are traditionally based on the one-target-one-drug paradigm, but effective treatment of complex neurological disorders generally requires modulation of several signaling pathways. In publication I, dual-target ligands that activate the D2 dopamine receptor (D2R) and antagonize the A2A adenosine receptor (A2AAR) were designed through a structure-based approach. Both GPCRs are relevant for Parkinson’s disease (PD) and animal studies support that interactions with these targets induce neuroprotection while eliciting a synergistic therapeutic effect. One of the designed ligands was shown to yield an antiparkinsonian effect in a rodent model. Publication II focuses on the identification of negative allosteric modulators (NAMs) of the metabotropic glutamate receptor 5 (mGlu5) using structure-based virtual screening. Such modulators have been considered as a treatment of PD, fragile X syndrome and depression. The study discovered 11 allosteric modulators and four of these were also shown to be NAMs of mGlu5. Manuscript III describes the development of dual-target ligands acting as antagonists of the A2AAR and NAMs of mGlu5. Blocking the activity of both receptors has been shown to have a synergistic antiparkinsonian effect that could be both symptomatic and neuroprotective. In this study, virtual screening was used to discover drug-like compounds with submicromolar binding affinity to both targets. Publication IV presents a comprehensive review of SBDD targeting GPCRs of all classes with a specific focus on the method of molecular docking. Publication V describes a program for automatic validation of X-ray crystal structures. Possible applications involve assessment of protein structures used in SBDD or the generation of high-quality test sets for the evaluation of molecular docking methods. The results of this thesis illustrate that structure-based virtual screening is a versatile tool to discover ligands with tailored pharmacological properties.
|
|
| 11. |
- Knopman, David S., et al.
(författare)
-
The National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease : Perspectives from the Research Roundtable
- 2018
-
Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:4, s. 563-575
-
Forskningsöversikt (refereegranskat)abstract
- The Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the “A, T, N System” (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development. In addition, challenges and barriers to the potential adoption of this new framework will be discussed. Finally, future directions for research will be proposed.
|
|
| 12. |
- Kolb, Gundula, et al.
(författare)
-
Dynamic Responses in a Plant-Insect System to Fertilization by Cormorant Feces
- 2015
-
Ingår i: Insects. - : MDPI AG. - 2075-4450. ; 6:2, s. 419-431
-
Tidskriftsartikel (refereegranskat)abstract
- Theoretical arguments suggest that increased plant productivity may not only increase consumer densities but also their fluctuations. While increased consumer densities are commonly observed in fertilization experiments, experiments are seldom performed at a spatial and temporal scale where effects on population fluctuations may be observed. In this study we used a natural gradient in soil fertility caused by cormorant nesting. Cormorants feed on fish but defecate on their nesting islands. On these islands we studied soil nutrient availability, plant nutrient content and the density of Galerucella beetles, main herbivores feeding on Lythrum salicaria. In a common garden experiment, we followed larval development on fertilized plants and estimated larval stoichiometry. Soil nutrient availability varied among islands, and several cormorant islands had very high N and P soil content. Plant nutrient content, however, did not vary among islands, and there was no correlation between soil and plant nutrient contents. Beetle densities increased with plant nutrient content in the field study. However, there was either no effect on temporal fluctuations in beetle density or that temporal fluctuations decreased (at high P). In the common garden experiment, we found limited responses in either larval survival or pupal weights to fertilization. A possible mechanism for the limited effect of fertilization on density fluctuations may be that the distribution of L. salicaria on nesting islands was restricted to sites with a lower N and P content, presumably because high N loads are toxic.
|
|
| 13. |
- Kolb, Gundula S., et al.
(författare)
-
Ecological Stoichiometry and Density Responses of Plant-Arthropod Communities on Cormorant Nesting Islands
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4, s. e61772-
-
Tidskriftsartikel (refereegranskat)abstract
- Seabirds deposit large amounts of nutrient rich guano on their nesting islands. The increased nutrient availability strongly affects plants and consumers. Consumer response differs among taxonomic groups, but mechanisms causing these differences are poorly understood. Ecological stoichiometry might provide tools to understand these mechanisms. ES suggests that nutrient rich taxa are more likely to be nutrient limited than nutrient poorer taxa and are more favored under nutrient enrichment. Here, we quantified differences in the elemental composition of soil, plants, and consumers between islands with and without nesting cormorant colonies and tested predictions made based on ES by relating the elemental composition and the eventual mismatch between consumer and resource stoichiometry to observed density differences among the island categories. We found that nesting cormorants radically changed the soil nutrient content and thereby indirectly plant nutrient content and resource quality to herbivores. In contrast, consumers showed only small differences in their elemental composition among the island categories. While we cannot evaluate the cause of the apparent homeostasis of invertebrates without additional data, we can conclude that from the perspective of the next trophic level, there is no difference in diet quality (in terms of N and P content) between island categories. Thus, bottom-up effects seemed mainly be mediated via changes in resource quantity not quality. Despite a large potential trophic mismatch we were unable to observe any relation between the invertebrate stoichiometry and their density response to nesting cormorant colonies. We conclude that in our system stoichiometry is not a useful predictor of arthropod responses to variation in resource nutrient content. Furthermore, we found no strong evidence that resource quality was a prime determinant of invertebrate densities. Other factors like resource quantity, habitat structure and species interactions might be more important or masked stoichiometric effects.
|
|
| 14. |
- Kolb, Gundula S., 1978-, et al.
(författare)
-
Ecological stoichiometry and homeostasis of plants and invertebrates on and nearby heavily fertilized cormorant nesting islands
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Ecological stoichiometry has generalized the fundamental role of individual nutrient demand in all ecological processes and interactions. It implies that the elemental composition (C:N:P) of a consumer relative to the C:N:P of its resource determines its growth rate and thus secondary productivity. A central, but recently questioned, principle of ecological stoichiometry is the assumption that heterotrophs, in contrast to autotrophs, keep their elemental composition strongly homeostatic. Since neither the relationship between consumer C:N:P and its numeric response to changes in resource C:N:P nor the C:N:P homeostasis of arthropods have been extensively studied for arthropods, we used a natural gradient of N and P loads, in form of seabird and non-seabird islands, to investigate the stoichiometry and homeostasis of primary producers and invertebrates, both on and around islands. We then looked for causal relationships between stoichiometry and the level of homeostasis of a taxonomic group, respectively, and observed numerical responses to seabird fertilization. We found in accordance to principal theories that invertebrates, generally, strongly regulated their stoichiometry while autotrophs were stoichiometrically plastic. Thus, we found no causal relationship between consumer homeostasis and displayed numeric responses. Furthermore, we found only weak support for the hypothesis that the C:N:P of a taxa determines its numeric response to increased resource nutrient content (lepidopteran larvae had high P:C and high abundance on P-rich cormorant islands). We conclude that other species traits than nutrient content mainly determine the success of a taxa in a certain environment. Additionally, due to the strong effects of different level of homeostasis on ecological interactions, food web dynamics and nutrient cycles, we underline the need of further studies on the homeostasis of arthropods.
|
|
| 15. |
- Kolb, Gundula S., et al.
(författare)
-
Effects of Nesting Cormorants (Phalacrocorax carbo) on Soil Chemistry, Microbial Communities and Soil Fauna
- 2015
-
Ingår i: Ecosystems. - : Springer Science and Business Media LLC. - 1432-9840 .- 1435-0629. ; 18:4, s. 643-657
-
Tidskriftsartikel (refereegranskat)abstract
- Seabirds act as vectors transporting marine nutrients to land by feeding on fish while nesting and roosting on islands. By depositing large amounts of nutrient-rich guano on their nesting islands they strongly affect island soils, vegetation and consumers. However, few studies have investigated how nesting seabirds affect soil communities. In this study, we investigated how cormorant nesting colonies affect soil chemistry, soil microbes and soil and litter fauna on their nesting islands in the Stockholm archipelago, Sweden. We found that cormorant colonies strongly increase organic soil N and P concentrations, and the effect is stronger close to cormorant nests. Microbial communities were studied by extracting phospholipid fatty acids (PLFA) from the soil. The total amounts of PLFA and the amount of PLFA indicating bacterial biomass were lower on active cormorant islands than on reference islands. Furthermore, PLFA structure and thus microbial community structure differed between cormorant and reference islands. Among ten investigated soil and litter arthropod groups three groups (Thysanoptera, Araneae and Oribatida) showed lower densities and one group (Astigmata) showed higher densities in soils on active cormorant than on reference islands. Some arthropod groups showed strong spatial variation on the cormorant islands. Astigmata, Mesostigmata and Diptera showed higher densities in soil samples close to cormorant nests, whereas Oribatida, Collembola and Hemiptera showed lower densities in litter samples close to cormorant nests than in samples taken 3-20 m away from nests. Overall, the cormorant colonies strongly affected soil ecosystems of their nesting islands, but causal correlations between arthropod densities and soil factors were difficult to reveal. One likely reason may be that nesting cormorant islands are very heterogeneous habitats showing large spatial variation in both soil properties as well as fauna densities.
|
|
| 16. |
- Kolb, Gundula S., et al.
(författare)
-
Effects of seabird nesting colonies on algae and aquatic invertebrates in coastal waters
- 2010
-
Ingår i: Marine Ecology Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 417, s. 287-300
-
Tidskriftsartikel (refereegranskat)abstract
- Seabirds concentrate nutrients from large marine areas on their nesting islands. The high nutrient load may cause runoff into surrounding waters and affect marine communities in similar ways to those reported from marine fertilization experiments. In order to test if cormorant colonies affect algae and invertebrates in surrounding coastal waters, we collected Fucus vesiculosus fronds, its epiphytic algae, and associated invertebrate fauna near abandoned and active cormorant nesting islands as well as reference islands without nesting cormorants in the Stockholm archipelago in the northern Baltic Sea, Sweden. First, we showed, with delta N-15 analyses, that ornithogenic nitrogen provided a significant nitrogen source for algae and invertebrate consumers near islands with high nest density. Second, the nitrogen and phosphorus content of algae near active cormorant islands with high nest density was elevated, and epiphytic algae increased relative to F. vesiculosus. Third, 3 of 5 invertebrate taxa (Jaera albifrons, Gammarus spp., and Chironomidae) showed increased biomasses near islands with high nest density; but, contrary to former fertilization studies, only J. albifrons increased in abundance compared to reference islands. We conclude that runoff from seabird colonies has a profound effect on primary producers and some consumers in the surrounding water, but only if the colonies exceed a certain nest density. Thus, seabirds not only affect marine communities via top-town forces as commonly assumed, but also via bottom-up forces by concentrating nutrients around their nesting islands. Consequently, seabird islands can be seen as natural fertilization experiments and give important insights to the effects of eutrophication of marine systems.
|
|
| 17. |
- Kolb, Gundula S., 1978-, et al.
(författare)
-
Effects of seabird nesting colonies on algae and aquatic invertebrates in coastal waters
-
Ingår i: Marine Ecology Progress Series. - 0171-8630 .- 1616-1599.
-
Tidskriftsartikel (refereegranskat)abstract
- Seabirds concentrate marine nutrients, from large marine areas, on their nesting islands. The high nutrient load may cause runoff into surrounding waters and affect marine communities in similar ways as reported from marine fertilization experiments. In order to test if cormorant colonies affect algae and invertebrates in surrounding coastal waters, we collected Fucus vesiculosus fronds, its epiphytic algae and associated invertebrate fauna near abandoned and active cormorant nesting islands and reference islands without nesting cormorants in the Stockholm archipelago in the northern Baltic Proper, Sweden. First, we showed, with δ15N analyses, that ornithogenic nitrogen provided a significant nitrogen source for algae and invertebrate consumers near islands with high nest density. Second, the nitrogen and phosphorus content of algae near active cormorant islands with high nest density was elevated and epiphytic algae increased relative to Fucus. Third, 3 of 5 invertebrate taxa (Jaera albifrons, Gammarus spp. and Chironomidae) showed increased biomasses near islands with high nest density, but contrary to earlier fertilization studies only J. albifrons increased in abundance compared to reference islands. We conclude that runoff from seabird colonies has a profound effect on primary producers and some consumers in the surrounding water, but only if the colonies exceed a certain nest density. Thus, seabirds not only affect marine communities via top-town forces as commonly assumed, but also via bottom-up forces by concentrating nutrients around their nesting islands. Consequently, seabird islands can be seen as natural fertilization experiments and give important insights in the effects of eutrophication of marine systems.
|
|
| 18. |
- Kolb, Gundula S., 1978-
(författare)
-
The impact of cormorant nesting colonies on plants and arthropods
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Seabirds concentrate large amounts of marine nutrients on their nesting islands. This nutrient input can have large consequences for island food webs and community structure. The high nutrient load may also cause runoff into surrounding waters and affect marine communities. In my thesis, I studied the effect of cormorant nesting colonies on the stoichiometry, abundance, species richness, and species composition of plants, algae, and invertebrates on land and in costal waters and investigated if differences in the elemental composition or homeostasis can explain differences in the numerical response among invertebrate groups. δ15N analysis indicated that ornithogenic nitrogen provided a significant nitrogen source for plants and arthropods on nesting islands and around high nest density islands also for brackish algae and invertebrates. Furthermore, nutrient runoff created a potential feed-back loop to spiders via chironomids. Cormorant nutrient input changed island vegetation and increased plant P and N content and epiphytic algae:Fucus ratio, but decreased plant species richness and vegetation cover. Invertebrates responded indirectly to these qualitative and quantitative changes in their food source and habitat, but also directly to cormorant subsidies. However not all taxonomic and feeding groups were affected and responses were both positive and negative. Differences in the numerical response among taxonomic groups could not be explained by differences in the level of homeostasis, since, generally, all invertebrates were strongly homeostatic. Similarly, consumer nutrient content was a poor predictor for displayed responses. I conclude that cormorant colonies have strong impacts on island vegetation and some consumer groups. However, even if they can decrease the species richness of some organism groups on their nesting islands, they increase the habitat heterogeneity in an archipelago and thus may increase the regional species diversity.
|
|
| 19. |
- Kolb, Gundula S., et al.
(författare)
-
The impact of cormorants on plant–arthropod food webs on their nesting islands
- 2010
-
Ingår i: Ecosystems (New York. Print). - : Springer Science and Business Media LLC. - 1432-9840 .- 1435-0629. ; 13:3, s. 353-366
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigated the effects of cormorant colonies on plant–arthropod island food webs, the consequences of nutrient-rich runoff on marine communities, and feedback loops from marine to terrestrial ecosystems. Terrestrial plant responses were as expected, with the highest plant biomass on islands with low nest density and the highest nitrogen (N) content on islands with high nest density. In contrast to our hypothesis, we found no uniform density response across guilds. Among herbivores, the variable responses may depend on the relative importance of plant quality or quantity. As expected, nutrient-rich runoff entered water bodies surrounding cormorant nesting islands, but only at high nest density, and increased the density of emerging insects. This created a potential feed-back loop to spiders (major terrestrial predators), where stable isotope analyses suggested great use of chironomids. Contrary to our expectation, this potential feed-back did not result in the highest spider density on islands with a high cormorant nest density. Web spiders showed no changes in density on active cormorant islands, and lycosids were actually less abundant on active cormorant islands compared to reference islands. The variable response of spiders despite increased dipteran densities, and also in other consumer groups, may be due to direct negative effects of cormorants on soil chemistry, vegetation cover, and other density regulating forces (for example, top–down forces) not studied here. This study highlights the importance of including processes in the surrounding marine ecosystem to understand the impacts of seabirds on the food web structures of their nesting islands.
|
|
| 20. |
- Kolb, Gundula S., et al.
(författare)
-
The impact of nesting cormorants on plant and arthropod diversity
- 2012
-
Ingår i: Ecography. - : Wiley. - 0906-7590 .- 1600-0587. ; 35:8, s. 726-740
-
Tidskriftsartikel (refereegranskat)abstract
- Seabirds can strongly affect several major factors correlated with species diversity by concentrating marine nutrients on their nesting islands and by physically disturbing island vegetation. In this study, we investigated the effects of nesting cormorants on the abundance, species richness, and composition of plants and arthropods (Coleoptera, Heteroptera, Araneae, and Chironomidae) on islands in Stockholm archipelago, Sweden. Nesting cormorants negatively affected plant species richness and vegetation cover and that changed plant species composition. The effect of nesting cormorants on island arthropods varied between feeding groups and sampling methods. Most orders did not change in abundance or species richness but some, such as coleopterans and spiders changed in species composition. Herbivorous coleopterans were generally negatively affected by cormorants whereas fungivorous species and scavengers were generally positively affected. In structural equation modeling we found that the effect of cormorants was sometimes direct, such as on scavengers, but many effects on island consumers were mediated by changes in vegetation caused by cormorant presence. Overall, arthropod communities were highly dissimilar between cormorant and reference islands, and we therefore conclude that nesting cormorants not only affect the diversity of their nesting islands but also of the archipelago as a whole. The total diversity in the archipelago may increase through regional increased habitat heterogeneity and by adding species which are favored by seabirds (e.g. scavenging and fungivorous coleopterans).
|
|
| 21. |
- Kolb, Gundula S., 1978-, et al.
(författare)
-
The impact of nesting cormorants on plant and arthropod diversity
-
Tidskriftsartikel (refereegranskat)abstract
- Seabirds can strongly affect major factors correlated with species diversity – primary productivity, heterogeneity, and disturbance – on their nesting islands through the concentration of marine nutrients and physical disturbing island vegetation. In this study, we investigated the effects of nesting cormorants on the abundance, species richness, and composition of plants and arthropods (Coleoptera, Heteroptera, Araneae, and Chironomidae) on islands in Stockholm archipelago, Sweden. We found that cormorants had a negative effect on plant species richness and vegetation cover and that they changed plant species composition. Plant biomass showed no linear correlation with nest density when considering all islands studied, but was negatively correlated with nest density when considering only cormorant islands. The effect of nesting cormorants on island arthropods varied across feeding groups and sampling methods. Coleopterans and cursorial spiders responded with shifts in species richness and composition, and several coleopteran feeding groups and chironomids also changed in abundance. The abundance and species richness of saprophagous and fungivorous coleopterans were higher on active cormorant islands than on reference islands, while the abundance and species richness of herbivorous coleopterans and the species richness of cursorial spiders were negatively correlated with nest density. In structural equation modeling we found that some feeding groups were directly affected by nest density, but that many of the effects of seabirds on island consumers were mediated by changes in vegetation. We conclude that nesting cormorants affect the diversity of their nesting islands and the archipelago as a whole. Although cormorant colonies can decrease the species diversity of plants and some invertebrate groups on their nesting islands, the total diversity in the archipelago may increase through regional increased habitat heterogeneity and by adding species which are favored by seabirds (e.g., saprophagous and fungivorous coleopterans).
|
|
| 22. |
- Kyriakou, Charalampia, et al.
(författare)
-
High-dose therapy and autologous stem-cell transplantation in angioimmunoblastic lymphoma : complete remission at transplantation is the major determinant of Outcome-Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
- 2008
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 26:2, s. 218-224
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Patients with angioimmunoblastic T-cell lymphoma (AITL) have poor prognoses with current conventional chemotherapy. The aim of this study was to evaluate the effect of high-dose therapy (HDT) followed by autologous stem-cell transplantation (ASCT) on patients with AITL. PATIENTS AND METHODS: We report a retrospective, multicenter study of 146 patients with AITL who received ASCT. The source of the stem cells was peripheral blood in 143 patients. The conditioning regimen varied, and 74% of the patients received carmustine and 1,3-bis(2-chloroethyl)-1-nitrosourea; etoposide; ara-C; and melphalan chemotherapy. RESULTS: After a median follow-up of 31 months (range, 3 to 174 months), 95 patients (65%) remained alive, and 51 patients (35%) died. Forty-two patients died as a result of disease progression, and nine died as a result of regimen-related toxicity. The cumulative incidence of nonrelapse mortality was 5% and 7% at 12 and 24 months, respectively. The actuarial overall survival (OS) was 67% at 24 months and 59% at 48 months. The cumulative incidence of relapse was estimated at 40% and 51% at 24 and 48 months, respectively. Disease status at transplantation was the major factor that impacted outcome. Patients who received a transplant during first complete remission (CR) had significantly superior progression-free survival and OS. The estimated PFS rates for patients who received their transplants in CR were 70% and 56% at 24 and 48 months, respectively; 42% and 30% for patients with chemotherapy-sensitive disease at those time points, respectively; and 23% at both time points for patients with chemotherapy-refractory disease. CONCLUSION: This study shows that HDT and ASCT offers the possibility of long-term disease-free survival to patients with AITL. Early transplantation is necessary to achieve optimal results.
|
|
| 23. |
|
|
| 24. |
- LaRue, Jerry, et al.
(författare)
-
Symmetry-resolved CO desorption and oxidation dynamics on O/Ru(0001) probed at the C K-edge by ultrafast x-ray spectroscopy
- 2022
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 157:16
-
Tidskriftsartikel (refereegranskat)abstract
- We report on carbon monoxide desorption and oxidation induced by 400 nm femtosecond laser excitation on the O/Ru(0001) surface probed by time-resolved x-ray absorption spectroscopy (TR-XAS) at the carbon K-edge. The experiments were performed under constant background pressures of CO (6 × 10−8 Torr) and O2 (3 × 10−8 Torr). Under these conditions, we detect two transient CO species with narrow 2π* peaks, suggesting little 2π* interaction with the surface. Based on polarization measurements, we find that these two species have opposing orientations: (1) CO favoring a more perpendicular orientation and (2) CO favoring a more parallel orientation with respect to the surface. We also directly detect gas-phase CO2 using a mass spectrometer and observe weak signatures of bent adsorbed CO2 at slightly higher x-ray energies than the 2π* region. These results are compared to previously reported TR-XAS results at the O K-edge, where the CO background pressure was three times lower (2 × 10−8 Torr) while maintaining the same O2 pressure. At the lower CO pressure, in the CO 2π* region, we observed adsorbed CO and a distribution of OC–O bond lengths close to the CO oxidation transition state, with little indication of gas-like CO. The shift toward “gas-like” CO species may be explained by the higher CO exposure, which blocks O adsorption, decreasing O coverage and increasing CO coverage. These effects decrease the CO desorption barrier through dipole–dipole interaction while simultaneously increasing the CO oxidation barrier.
|
|
| 25. |
- Lukkarinen, Heikki, et al.
(författare)
-
Time Trends of Cerebrospinal Fluid Biomarkers of Neurodegeneration in Idiopathic Normal Pressure Hydrocephalus.
- 2021
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 80:4, s. 1629-1642
-
Tidskriftsartikel (refereegranskat)abstract
- Longitudinal changes in cerebrospinal fluid (CSF) biomarkers are seldom studied. Furthermore, data on biomarker gradient between lumbar (L-) and ventricular (V-) compartments seems to be discordant.To examine alteration of CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid-β (Aβ) aggregation, tau pathology, neurodegeneration, and early synaptic degeneration by CSF shunt surgery in idiopathic normal pressure hydrocephalus (iNPH) in relation to AD-related changes in brain biopsy. In addition, biomarker levels in L- and V-CSF were compared.L-CSF was collected prior to shunt placement and, together with V-CSF, 3-73 months after surgery. Thereafter, additional CSF sampling took place at 3, 6, and 18 months after the baseline sample from 26 iNPH patients with confirmed Aβ plaques in frontal cortical brain biopsy and 13 iNPH patients without Aβ pathology. CSF Amyloid-β42 (Aβ42), total tau (T-tau), phosphorylated tau (P-tau181), neurofilament light (NFL), and neurogranin (NRGN) were analyzed with customized ELISAs.All biomarkers but Aβ42 increased notably by 140-810% in L-CSF after CSF diversion and then stabilized. Aβ42 instead showed divergent longitudinal decrease between Aβ-positive and -negative patients in L-CSF, and thereafter increase in Aβ-negative iNPH patients in both L- and V-CSF. All five biomarkers correlated highly between V-CSF and L-CSF (Aβ42 R=0.87, T-tau R=0.83, P-tau R=0.92, NFL R=0.94, NRGN R=0.9; all p< 0.0001) but were systematically lower in V-CSF (Aβ42 14 %, T-tau 22%, P-tau 20%, NFL 32%, NRGN 19%). With APOE genotype-grouping, only Aβ42 showed higher concentration in non-carriers of allele ɛ4.Longitudinal follow up shows that after an initial post-surgery increase, T-tau, P-tau, and NRGN are stable in iNPH patients regardless of brain biopsy Aβ pathology, while NFL normalized toward its pre-shunt levels. Aβ42 as biomarker seems to be the least affected by the surgical procedure or shunt and may be the best predictor of AD risk in iNPH patients. All biomarker concentrations were lower in V- than L-CSF yet showing strong correlations.
|
|
| 26. |
- Nesti, Cedric, et al.
(författare)
-
Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size : a retrospective, Europe-wide, pooled cohort study
- 2023
-
Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 24:2, s. 187-194
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundAwareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1–2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1–2 cm in size in patients with or without right-sided hemicolectomy.MethodsIn this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1–2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693.Findings282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1–2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0–15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 –21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36–2·17]; p=0·71).InterpretationThis study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1–2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort.
|
|
| 27. |
- Niu, Shuli, et al.
(författare)
-
Thermal optimality of net ecosystem exchange of carbon dioxide and underlying mechanisms.
- 2012
-
Ingår i: New Phytologist. - : Wiley. - 1469-8137 .- 0028-646X. ; 194:3, s. 775-783
-
Tidskriftsartikel (refereegranskat)abstract
- • It is well established that individual organisms can acclimate and adapt to temperature to optimize their functioning. However, thermal optimization of ecosystems, as an assemblage of organisms, has not been examined at broad spatial and temporal scales. • Here, we compiled data from 169 globally distributed sites of eddy covariance and quantified the temperature response functions of net ecosystem exchange (NEE), an ecosystem-level property, to determine whether NEE shows thermal optimality and to explore the underlying mechanisms. • We found that the temperature response of NEE followed a peak curve, with the optimum temperature (corresponding to the maximum magnitude of NEE) being positively correlated with annual mean temperature over years and across sites. Shifts of the optimum temperature of NEE were mostly a result of temperature acclimation of gross primary productivity (upward shift of optimum temperature) rather than changes in the temperature sensitivity of ecosystem respiration. • Ecosystem-level thermal optimality is a newly revealed ecosystem property, presumably reflecting associated evolutionary adaptation of organisms within ecosystems, and has the potential to significantly regulate ecosystem-climate change feedbacks. The thermal optimality of NEE has implications for understanding fundamental properties of ecosystems in changing environments and benchmarking global models.
|
|
| 28. |
- Palumbo, Antonio, et al.
(författare)
-
Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials
- 2013
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 98:1, s. 87-94
-
Tidskriftsartikel (refereegranskat)abstract
- Treatment with melphalan-prednisone-thalidomide improves the outcome of patients with multiple myeloma and is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. A meta-analysis of data from individual patients (n=1680) in six randomized trials was performed, comparing the effects of melphalan-prednisone-thalidomide versus melphalan-prednisone. The main objective was to estimate the risk of serious adverse events and their impact on outcome. The primary endpoints were the 2-year cumulative incidence of grade 3-4 hematologic and non-hematologic toxicities. At least 75% of the grade 3-4 toxicities occurred during the first 6 months of treatment in both treatment groups. The cumulative incidence of grade 3-4 hematologic toxicities was higher in the melphalan-prednisone-thalidomide group than in the melphalan-prednisone group (28% versus 22%; HR 1.32, 95% CI 1.05-1.66) as was the cumulative incidence of non-hematologic toxicities (39% versus 17%, HR 2.78, 95% CI 2.21-3.50). Grade 3-4 non-hematologic toxicities were significantly increased in patients with poor Performance Status. Occurrence of grade 3-4 non-hematologic toxicities had a negative impact on both progression-free survival (HR 1.24, 95% CI 1.07-1.45) and overall survival, (HR 1.23, 95% CI 1.03-1.47). Besides toxicities, progression-free and overall survival were also negatively affected by advanced International Staging System stage, high creatinine levels and poor Performance Status. Age had a negative impact on survival as well. Although melphalan-prednisone-thalidomide improved outcome, it increased toxicities, especially non-hematologic ones. Serious non-hematologic toxicities, older age, poor Performance Status, and high creatinine levels negatively affected survival. (C) 2013 Ferrata Storti Foundation. This is an open-access paper. doi: 10.3324/haematol.2012.067058
|
|
| 29. |
- Panzitt, Katrin, et al.
(författare)
-
FXR-dependent Rubicon induction impairs autophagy in models of human cholestasis.
- 2020
-
Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 72:6, s. 1122-1131
-
Tidskriftsartikel (refereegranskat)abstract
- Cholestasis comprises a spectrum of liver diseases characterized by the accumulation of bile acids. Bile acids and activation of the farnesoid X receptor (FXR) can inhibit autophagy, a cellular self-digestion process necessary for cellular homeostasis and regeneration. In mice, autophagy appears to be impaired in cholestasis and induction of autophagy may reduce liver injury.Herein, we explored autophagy in human cholestasis invivo and investigated the underlying molecular mechanisms invitro. FXR chromatin immunoprecipitation-sequencing and qPCR were performed in combination with luciferase promoter studies to identify functional FXR binding targets in a human cholestatic liver sample.Autophagic processing appeared to be impaired in patients with cholestasis and in individuals treated with the FXR ligand obeticholic acid (OCA). Invitro, chenodeoxycholic acid and OCA inhibited autophagy at the level of autophagosome to lysosome fusion in an FXR-dependent manner. Rubicon, which inhibits autophago-lysosomal maturation, was identified as a direct FXR target that is induced in cholestasis and by FXR-agonistic bile acids. Genetic inhibition of Rubicon reversed the bile acid-induced impairment of autophagic flux. In contrast to OCA, ursodeoxycholic acid (UDCA), which is a non-FXR-agonistic bile acid, induced autophagolysosome formation independently of FXR, enhanced autophagic flux and was associated with reduced Rubicon levels.In models of human cholestasis, autophagic processing is impaired in an FXR-dependent manner, partly resulting from the induction of Rubicon. UDCA is a potent inducer of hepatic autophagy. Manipulating autophagy and Rubicon may represent a novel treatment concept for cholestatic liver diseases.Autophagy, a cellular self-cleansing process, is impaired in various forms of human cholestasis. Bile acids, which accumulate in cholestatic liver disease, induce Rubicon, a protein that inhibits proper execution of autophagy. Ursodeoxycholic acid, which is the first-line treatment option for many cholestatic liver diseases, induces hepatic autophagy along with reducing Rubicon.
|
|
| 30. |
- Peaucelle, Marc, et al.
(författare)
-
Covariations between plant functional traits emerge from constraining parameterization of a terrestrial biosphere model
- 2019
-
Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 28:9, s. 1351-1365
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: The mechanisms of plant trait adaptation and acclimation are still poorly understood and, consequently, lack a consistent representation in terrestrial biosphere models (TBMs). Despite the increasing availability of geo-referenced trait observations, current databases are still insufficient to cover all vegetation types and environmental conditions. In parallel, the growing number of continuous eddy-covariance observations of energy and CO2 fluxes has enabled modellers to optimize TBMs with these data. Past attempts to optimize TBM parameters mostly focused on model performance, overlooking the ecological properties of ecosystems. The aim of this study was to assess the ecological consistency of optimized trait-related parameters while improving the model performances for gross primary productivity (GPP) at sites. Location: Worldwide. Time period: 1992–2012. Major taxa studied: Trees and C3 grasses. Methods: We optimized parameters of the ORCHIDEE model against 371 site-years of GPP estimates from the FLUXNET network, and we looked at global covariation among parameters and with climate. Results: The optimized parameter values were shown to be consistent with leaf-scale traits, in particular, with well-known trade-offs observed at the leaf level, echoing the leaf economic spectrum theory. Results showed a marked sensitivity of trait-related parameters to local bioclimatic variables and reproduced the observed relationships between traits and climate. Main conclusions: Our approach validates some biological processes implemented in the model and enables us to study ecological properties of vegetation at the canopy level, in addition to some traits that are difficult to observe experimentally. This study stresses the need for: (a) implementing explicit trade-offs and acclimation processes in TBMs; (b) improving the representation of processes to avoid model-specific parameterization; and (c) performing systematic measurements of traits at FLUXNET sites in order to gather information on plant ecophysiology and plant diversity, together with micro-meteorological conditions.
|
|
| 31. |
- Phillip, Moshe, et al.
(författare)
-
Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes
-
Ingår i: Diabetes Care. - 1935-5548.
-
Tidskriftsartikel (refereegranskat)abstract
- Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings. To inform this monitoring, JDRF, in conjunction with international experts and societies, developed consensus guidance. Broad advice from this guidance includes the following: 1) partnerships should be fostered between endocrinologists and primary care providers to care for people who are IAb+; 2) when people who are IAb+ are initially identified, there is a need for confirmation using a second sample; 3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; 4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; 5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and 6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasizes significant unmet needs for further research on early-stage type 1 diabetes to increase the rigor of future recommendations and inform clinical care.
|
|
| 32. |
- Phillip, Moshe, et al.
(författare)
-
Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes
-
Ingår i: Diabetologia. - 1432-0428.
-
Tidskriftsartikel (refereegranskat)abstract
- Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk of (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb+; (2) when people who are IAb+ are initially identified there is a need for confirmation using a second sample; (3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.
|
|
| 33. |
- Shi, Liu, et al.
(författare)
-
Replication study of plasma proteins relating to Alzheimer's pathology.
- 2021
-
Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279 .- 1552-5260. ; 17:9, s. 1452-1464
-
Tidskriftsartikel (refereegranskat)abstract
- This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the "ATN" (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis.Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively.Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and "N" varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis.Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.
|
|
| 34. |
- Sommer, Martha E., et al.
(författare)
-
The European Research Network on Signal Transduction (ERNEST) : Toward a Multidimensional Holistic Understanding of G Protein-Coupled Receptor Signaling
- 2020
-
Ingår i: ACS Pharmacology & Translational Science. - : American Chemical Society (ACS). - 2575-9108. ; 3:2, s. 361-370
-
Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) are intensively studied due to their therapeutic potential as drug targets. Members of this large family of transmembrane receptor proteins mediate signal transduction in diverse cell types and play key roles in human physiology and health. In 2013 the research consortium GLISTEN (COST Action CM1207) was founded with the goal of harnessing the substantial growth in knowledge of GPCR structure and dynamics to push forward the development of molecular modulators of GPCR function. The success of GLISTEN, coupled with new findings and paradigm shifts in the field, led in 2019 to the creation of a related consortium called ERNEST (COST Action CA18133). ERNEST broadens focus to entire signaling cascades, based on emerging ideas of how complexity and specificity in signal transduction are not determined by receptor-ligand interactions alone. A holistic approach that unites the diverse data and perspectives of the research community into a single multidimensional map holds great promise for improved drug design and therapeutic targeting.
|
|
| 35. |
- Strandmark, Alma, et al.
(författare)
-
Climate change effects on the Baltic Sea borderland between land and sea
- 2015
-
Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 44, s. s28-S38
-
Tidskriftsartikel (refereegranskat)abstract
- Coastal habitats are situated on the border between land and sea, and ecosystem structure and functioning is influenced by both marine and terrestrial processes. Despite this, most scientific studies and monitoring are conducted either with a terrestrial or an aquatic focus. To address issues concerning climate change impacts in coastal areas, a cross-ecosystem approach is necessary. Since habitats along the Baltic coastlines vary in hydrology, natural geography, and ecology, climate change projections for Baltic shore ecosystems are bound to be highly speculative. Societal responses to climate change in the Baltic coastal ecosystems should have an ecosystem approach and match the biophysical realities of the Baltic Sea area. Knowledge about ecosystem processes and their responses to a changing climate should be integrated within the decision process, both locally and nationally, in order to increase the awareness of, and to prepare for climate change impacts in coastal areas of the Baltic Sea.
|
|
| 36. |
- Therriault, Joseph, et al.
(författare)
-
Association of Phosphorylated Tau Biomarkers With Amyloid Positron Emission Tomography vs Tau Positron Emission Tomography.
- 2022
-
Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 80:2, s. 188-99
-
Tidskriftsartikel (refereegranskat)abstract
- The recent proliferation of phosphorylated tau (p-tau) biomarkers has raised questions about their preferential association with the hallmark pathologies of Alzheimer disease (AD): amyloid-β plaques and tau neurofibrillary tangles.To determine whether cerebrospinal fluid (CSF) and plasma p-tau biomarkers preferentially reflect cerebral β-amyloidosis or neurofibrillary tangle aggregation measured with positron emission tomography (PET).This was a cross-sectional study of 2 observational cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) study, with data collected between October 2017 and August 2021, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), with data collected between September 2015 and November 2019. TRIAD was a single-center study, and ADNI was a multicenter study. Two independent subsamples were derived from TRIAD. The first TRIAD subsample comprised individuals assessed with CSF p-tau (p-tau181, p-tau217, p-tau231, p-tau235), [18F]AZD4694 amyloid PET, and [18F]MK6240 tau PET. The second TRIAD subsample included individuals assessed with plasma p-tau (p-tau181, p-tau217, p-tau231), [18F]AZD4694 amyloid PET, and [18F]MK6240 tau PET. An independent cohort from ADNI comprised individuals assessed with CSF p-tau181, [18F]florbetapir PET, and [18F]flortaucipir PET. Participants were included based on the availability of p-tau and PET biomarker assessments collected within 9 months of each other. Exclusion criteria were a history of head trauma or magnetic resonance imaging/PET safety contraindications. No participants who met eligibility criteria were excluded.Amyloid PET, tau PET, and CSF and plasma assessments of p-tau measured with single molecule array (Simoa) assay or enzyme-linked immunosorbent assay.Associations between p-tau biomarkers with amyloid PET and tau PET.A total of 609 participants (mean [SD] age, 66.9 [13.6] years; 347 female [57%]; 262 male [43%]) were included in the study. For all 4 phosphorylation sites assessed in CSF, p-tau was significantly more closely associated with amyloid-PET values than tau-PET values (p-tau181 difference, 13%; 95% CI, 3%-22%; P=.006; p-tau217 difference, 11%; 95% CI, 3%-20%; P=.003; p-tau231 difference, 15%; 95% CI, 5%-22%; P<.001; p-tau235 difference, 9%; 95% CI, 1%-19%; P=.02) . These results were replicated with plasma p-tau181 (difference, 11%; 95% CI, 1%-22%; P=.02), p-tau217 (difference, 9%; 95% CI, 1%-19%; P=.02), p-tau231 (difference, 13%; 95% CI, 3%-24%; P=.009), and CSF p-tau181 (difference, 9%; 95% CI, 1%-21%; P=.02) in independent cohorts.Results of this cross-sectional study of 2 observational cohorts suggest that the p-tau abnormality as an early event in AD pathogenesis was associated with amyloid-β accumulation and highlights the need for careful interpretation of p-tau biomarkers in the context of the amyloid/tau/neurodegeneration, or A/T/(N), framework.
|
|
| 37. |
- Wagner, Kevin, et al.
(författare)
-
Imaging low-mass planets within the habitable zone of α Centauri
- 2021
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Giant exoplanets on wide orbits have been directly imaged around young stars. If the thermal background in the mid-infrared can be mitigated, then exoplanets with lower masses can also be imaged. Here we present a ground-based mid-infrared observing approach that enables imaging low-mass temperate exoplanets around nearby stars, and in particular within the closest stellar system, alpha Centauri. Based on 75-80% of the best quality images from 100h of cumulative observations, we demonstrate sensitivity to warm sub-Neptune-sized planets throughout much of the habitable zone of alpha Centauri A. This is an order of magnitude more sensitive than state-of-the-art exoplanet imaging mass detection limits. We also discuss a possible exoplanet or exozodiacal disk detection around alpha Centauri A. However, an instrumental artifact of unknown origin cannot be ruled out. These results demonstrate the feasibility of imaging rocky habitable-zone exoplanets with current and upcoming telescopes. Imaging of low-mass exoplanets can be achieved once the thermal background in the mid-infrared (MIR) wavelengths can be mitigated. Here, the authors present a ground-based MIR observing approach enabling imaging low-mass temperate exoplanets around nearby stars.
|
|
