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1.
  • Householder, John Ethan, et al. (författare)
  • One sixth of Amazonian tree diversity is dependent on river floodplains
  • 2024
  • Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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2.
  • Luize, Bruno Garcia, et al. (författare)
  • Geography and ecology shape the phylogenetic composition of Amazonian tree communities
  • 2024
  • Ingår i: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
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3.
  • Santangelo, James S., et al. (författare)
  • Global urban environmental change drives adaptation in white clover
  • 2022
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
  • Tidskriftsartikel (refereegranskat)abstract
    • Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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4.
  • ter Steege, Hans, et al. (författare)
  • Mapping density, diversity and species-richness of the Amazon tree flora
  • 2023
  • Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution. A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.
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5.
  • Cruz, Raquel, et al. (författare)
  • Novel genes and sex differences in COVID-19 severity
  • 2022
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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6.
  • Garcia-Longoria, Luz, et al. (författare)
  • Diversity and host assemblage of avian haemosporidians in different terrestrial ecoregions of Peru
  • 2022
  • Ingår i: Current Zoology. - : Oxford University Press (OUP). - 1674-5507 .- 2396-9814. ; 68:1, s. 27-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Characterizing the diversity and structure of host-parasite communities is crucial to understanding their eco-evolutionary dynamics. Malaria and related haemosporidian parasites are responsible for fitness loss and mortality in bird species worldwide. However, despite exhibiting the greatest ornithological biodiversity, avian haemosporidians from Neotropical regions are quite unexplored. Here, we analyze the genetic diversity of bird haemosporidian parasites (Plasmodium and Haemoproteus) in 1,336 individuals belonging to 206 bird species to explore for differences in diversity of parasite lineages and bird species across 5 well-differentiated Peruvian ecoregions. We detected 70 different haemosporidian lineages infecting 74 bird species. We showed that 25 out of the 70 haplotypes had not been previously recorded. Moreover, we also identified 81 new host-parasite interactions representing new host records for these haemosporidian parasites. Our outcomes revealed that the effective diversity (as well as the richness, abundance, and Shannon-Weaver index) for both birds and parasite lineages was higher in Amazon basin ecoregions. Furthermore, we also showed that ecoregions with greater diversity of bird species also had high parasite richness, hence suggesting that host community is crucial in explaining parasite richness. Generalist parasites were found in ecoregions with lower bird diversity, implying that the abundance and richness of hosts may shape the exploitation strategy followed by haemosporidian parasites. These outcomes reveal that Neotropical region is a major reservoir of unidentified haemosporidian lineages. Further studies analyzing host distribution and specificity of these parasites in the tropics will provide important knowledge about phylogenetic relationships, phylogeography, and patterns of evolution and distribution of haemosporidian parasites.
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7.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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8.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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9.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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11.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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12.
  • Matuozzo, Daniela, et al. (författare)
  • Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
  • 2023
  • Ingår i: Genome medicine. - 1756-994X. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in~80% of cases.We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1×10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1×10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4×10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7×10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68×10-5).Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60years old.
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13.
  • Tavares, Julia, et al. (författare)
  • Basin-wide variation in tree hydraulic safety margins predicts the carbon balance of Amazon forests
  • 2023
  • Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 617:7959, s. 111-117
  • Tidskriftsartikel (refereegranskat)abstract
    • Tropical forests face increasing climate risk(1,2), yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, ?(50)) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk(3-5), little is known about how these vary across Earth's largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters ?(50) and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both ?(50) and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM(50 )forests. We propose that this may be associated with a growth-mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon(6,7), with strong implications for the Amazon carbon sink.
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14.
  • Yushkevich, Paul A., et al. (författare)
  • Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe
  • 2021
  • Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144:9, s. 2784-2797
  • Tidskriftsartikel (refereegranskat)abstract
    • Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual and group levels. Group-level maps were obtained in the space of an in vivo brain template, and neurofibrillary tangles were measured in specific anatomical regions defined in this template. Three-dimensional maps of neurofibrillary tangle burden revealed significant variation along the anterior-posterior axis. While early neurofibrillary tangle pathology is thought to be confined to the transentorhinal region, we found similar levels of burden in this region and other medial temporal lobe subregions, including amygdala, temporopolar cortex, and subiculum/cornu ammonis 1 hippocampal subfields. Overall, the three-dimensional maps of neurofibrillary tangle burden presented here provide more complete information about the distribution of this neurodegenerative pathology in the region of the cortex where it first emerges in Alzheimer's disease, and may help inform the field about the patterns of pathology spread, as well as support development and validation of neuroimaging biomarkers.
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15.
  • Abalde, Samuel, et al. (författare)
  • Hidden species diversity and mito-nuclear discordance within the Mediterranean cone snail, Lautoconus ventricosus
  • 2023
  • Ingår i: Molecular Phylogenetics and Evolution. - 1055-7903 .- 1095-9513. ; 186, s. 107838-107838
  • Tidskriftsartikel (refereegranskat)abstract
    • The Mediterranean cone snail, Lautoconus ventricosus, is currently considered a single species inhabiting the whole Mediterranean basin and the adjacent Atlantic coasts. Yet, no population genetic study has assessed its taxonomic status. Here, we collected 245 individuals from 75 localities throughout the Mediterranean Sea and used cox1 barcodes, complete mitochondrial genomes, and genome skims to test whether L. ventricosus represents a complex of cryptic species. The maximum likelihood phylogeny based on complete mitochondrial genomes recovered six main clades (hereby named blue, brown, green, orange, red, and violet) with sufficient sequence divergence to be considered putative species. On the other hand, phylogenomic analyses based on 437 nuclear genes only recovered four out of the six clades: blue and orange clades were thoroughly mixed and the brown one was not recovered. This mito-nuclear discordance revealed instances of incomplete lineage sorting and introgression, and may have caused important differences in the dating of main cladogenetic events. Species delimitation tests proposed the existence of at least three species: green, violet, and red + blue + orange (i.e., cyan). Green plus cyan (with sympatric distributions) and violet, had West and East Mediterranean distributions, respectively, mostly separated by the Siculo-Tunisian biogeographical barrier. Morphometric analyses of the shell using species hypotheses as factor and shell length as covariate showed that the discrimination power of the studied parameters was only 70.2%, reinforcing the cryptic nature of the uncovered species, and the importance of integrative taxonomic approaches considering morphology, ecology, biogeography, and mitochondrial and nuclear population genetic variation.
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16.
  • Barrera Diaz, Carlos Alberto, 1987-, et al. (författare)
  • Simulation-based multi-objective optimization for reconfigurable manufacturing system configurations analysis
  • 2020
  • Ingår i: Proceedings of the 2020 Winter Simulation Conference. - : IEEE. - 9781728194998 - 9781728195001 ; , s. 1527-1538, s. 1527-1538
  • Konferensbidrag (refereegranskat)abstract
    • The purpose of this study is to analyze the use of Simulation-Based Multi-Objective Optimization (SMO) for Reconfigurable Manufacturing System Configuration Analysis (RMS-CA). In doing so, this study addresses the need for efficiently performing RMS-CA with respect to the limited time for decision-making in the industry, and investigates one of the salient problems of RMS-CA: determining the minimum number of machines necessary to satisfy the demand. The study adopts an NSGA II optimization algorithm and presents two contributions to existing literature. Firstly, the study proposes a series of steps for the use of SMO for RMS-CA and shows how to simultaneously maximize production throughput, minimize lead time, and buffer size. Secondly, the study presents a qualitative comparison with the prior work in RMS-CA and the proposed use of SMO; it discusses the advantages and challenges of using SMO and provides critical insight for production engineers and managers responsible for production system configuration.
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17.
  • Brito-Zerón, Pilar, et al. (författare)
  • Mortality risk factors in primary Sjögren syndrome : a real-world, retrospective, cohort study
  • 2023
  • Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 61
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWhat baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score.MethodsIn this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables.FindingsBetween January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27–2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22–2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01–1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22–1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16–2) were independent predictors of SjS-related death.InterpretationThe key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS.
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18.
  • Burgos Macías, D. I., et al. (författare)
  • Determination of the seroprevalence of Leptospira spp. and the main serovars circulating in cattle in the province of Manabí, Ecuador
  • 2019
  • Ingår i: Revue scientifique et technique (International Office of Epizootics). - : The World Organisation for Animal Health (OIE). - 0253-1933. ; 38:3, s. 787-800
  • Tidskriftsartikel (refereegranskat)abstract
    • Leptospirosis is a transmissible zoonotic disease caused by pathogenic strains of the genus Leptospira. Clinical signs in cattle are fever, haematuria, haemoglobinuria, meningitis, abortion, birth of weak calves and infertility; in the most severe cases, it can cause death to the animal. The few studies conducted in Ecuador, and in particular the province of Manabí, have revealed varying prevalence rates, ranging from 35.8% to 75%. The objective of this study is to determine the seroprevalence of leptospirosis in cattle and to ascertain the main serovars circulating in the province of Manabí. A cross-sectional epidemiological study was conducted from November 2015 to March 2016, for which seven cantons were selected at random and a total of 854 animals from 67 herds were investigated. The samples were processed in the laboratories of the Animal Diagnostics Directorate of the Ecuadorian Agency for Agriculture Quality Assurance (AGROCALIDAD) in Tumbaco, using the microscopic agglutination test. The sera were analysed to check whether they contained any of the eight serovars of Leptospira interrogans circulating most frequently in the country: Canicola, Hardjo, Pomona, Icterohaemorrhagiae, Grippotyphosa, Wolffi, Bratislava and Copenhageni. Overall seroprevalence at herd level was 97.01%, with the most common serovars being Pomona, Icterohaemorrhagiae, Grippotyphosa, Bratislava and Canicola. It was concluded that there is high seroprevalence at herd level in the province of Manabí.
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19.
  • Ferrando, Carlos, et al. (författare)
  • Adjusting tidal volume to stress index in an open lung condition optimizes ventilation and prevents overdistension in an experimental model of lung injury and reduced chest wall compliance
  • 2015
  • Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The stress index ( SI), a parameter derived from the shape of the pressure-time curve, can identify injurious mechanical ventilation. We tested the hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung condition avoids hypoventilation while preventing overdistension in an experimental model of combined lung injury and low chest-wall compliance (Ccw). Methods: Lung injury was induced by repeated lung lavages using warm saline solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in 22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals were recruited and submitted to a positive end-expiratory pressure (PEEP) titration trial to find the PEEP level resulting in maximum compliance. During a subsequent four hours of mechanical ventilation, VT was adjusted to keep a plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between 0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a 'normal' PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In addition Computed Tomography (CT) data were acquired at end expiration and end inspiration in six animals. Results: PaCO2 was significantly higher in the Pplat-group (82 versus 53 mmHg, P = 0.01), with a resulting lower pH (7.19 versus 7.34, P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg-1, P = 0.002) and Pplat values (30 versus 35 cmH2O, P = 0.001) between the Pplat-group and SI-group respectively. SI (1.03 versus 0.99, P = 0.42) and end-inspiratory transpulmonary pressure (PTP) (17 versus 18 cmH2O, P = 0.42) were similar in the Pplat-and SI-groups respectively, without differences in overinflated lung areas at end-inspiration in both groups. Cytokines and histopathology showed no differences. Conclusions: Setting tidal volume to a non-injurious stress index in an open lung condition improves alveolar ventilation and prevents overdistension without increasing lung injury. This is in comparison with limited Pplat protective ventilation in a model of lung injury with low chest-wall compliance.
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20.
  • Flores-Copa, Vidal, et al. (författare)
  • Residual brewing yeast as substrate for co-production of cell biomass and biofilm using Candida maltosa SM4
  • 2021
  • Ingår i: Fermentation. - : MDPI. - 2311-5637. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Candida maltosa was cultivated in the liquid phase of residual brewing yeast, a major brewery residue, to produce biomass and biofilm. Using response surface methodology, the effect of two variables at two different levels was investigated. The independent variables were agitation speed (at 100 and 200 rpm), and aeration (at 1 and 3 L min−1). Aeration was identified to be important for the production of both biomass and biofilm, while agitation was the only factor significantly affecting biofilm production. The maximal production of biofilm (2.33 g L−1) was achieved for agitation of 200 rpm and aeration of 1 L min−1, while the maximum for biomass (16.97 g L−1) was reached for 100 rpm agitation and 3 L min−1 air flow. A logistic model applied to predict the growth of C. maltosa in the exponential phase and the biofilm production, showed a high degree of agreement between the prediction and the actual biomass measured experimentally. The produced biofilms were further characterized using Fourier-transform infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and Thermogravimetric Analysis (TGA). FTIR allowed the identification of methyl, carbonyl ester and sulfate groups, and revealed the presence of uronic acid moieties and glycosidic bonds. Water-retention ability up to relatively high temperatures was revealed by TGA, and that makes the produced biofilm suitable for production of hydrogels. SEM also gave indications on the hydrogel-forming potential of the biofilm.
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21.
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22.
  • Flores-Langarica, Adriana, et al. (författare)
  • Intestinal CD103+CD11b+ cDC2 conventional dendritic cells are required for primary CD4+ T and B cell responses to soluble flagellin
  • 2018
  • Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9:OCT
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic immunization with soluble flagellin (sFliC) from Salmonella Typhimurium induces mucosal responses, offering potential as an adjuvant platform for vaccines. Moreover, this engagement of mucosal immunity is necessary for optimal systemic immunity, demonstrating an interaction between these two semi-autonomous immune systems. Although TLR5 and CD103+CD11b+ cDC2 contribute to this process, the relationship between these is unclear in the early activation of CD4+ T cells and the development of antigen-specific B cell responses. In this work, we use TLR5-deficient mice and CD11c-cre.Irf4fl/fl mice (which have reduced numbers of cDC2, particularly intestinal CD103+CD11b+ cDCs), to address these points by studying the responses concurrently in the spleen and the mesenteric lymph nodes (MLN). We show that CD103+CD11b+ cDC2 respond rapidly and accumulate in the MLN after immunization with sFliC in a TLR5-dependent manner. Furthermore, we identify that whilst CD103+CD11b+ cDC2 are essential for the induction of primary T and B cell responses in the mucosa, they do not play such a central role for the induction of these responses in the spleen. Additionally, we show the involvement of CD103+CD11b+ cDC2 in the induction of Th2-associated responses. CD11c-cre.Irf4fl/fl mice showed a reduced primary FliC-specific Th2-associated IgG1 responses, but enhanced Th1-associated IgG2c responses. These data expand our current understanding of the mucosal immune responses promoted by sFliC and highlights the potential of this adjuvant for vaccine usage by taking advantage of the functionality of mucosal CD103+CD11b+ cDC2.
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23.
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24.
  • Haycock, Philip C., et al. (författare)
  • Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
  • 2017
  • Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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25.
  • Hernández-Jiménez, Macaarena, et al. (författare)
  • APRIL : A double-blind, placebo-controlled, randomized, Phase Ib/IIa clinical study of ApTOLL for the treatment of acute ischemic stroke
  • 2023
  • Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • In the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) and neuroprotective drugs is emerging as a promising therapeutic option for patients with acute ischemic stroke (AIS). In this context, ApTOLL, a Toll-like receptor 4 (TLR4) antagonist with proven neuroprotective effect in preclinical models of stroke and a very good pharmacokinetic and safety profile in healthy volunteers, is a promising first-in-class aptamer with the potential to address this huge unmet need. This protocol establishes the clinical trial procedures to conduct a Phase Ib/IIa clinical study (APRIL) to assess ApTOLL tolerability, safety, pharmacokinetics, and biological effect in patients with AIS who are eligible for EVT. This will be a multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to evaluate the administration of ApTOLL together with EVT in patients with AIS. The study population will be composed of men and non-pregnant women with confirmed AIS with a <6h window from symptoms onset to ApTOLL/placebo administration. The trial is currently being conducted and is divided into two parts: Phase Ib and Phase IIa. In Phase Ib, 32 patients will be allocated to four dose ascending levels to select, based on safety criteria, the best two doses to be administered in the following Phase IIa in which 119 patients will be randomized to three arms of treatment (dose A, dose B, and placebo).
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26.
  • Lam, Michael, et al. (författare)
  • The effect of the dental follicle volume of palatally impacted canines on the relative position of the adjacent teeth
  • 2024
  • Ingår i: EUROPEAN JOURNAL OF ORTHODONTICS. - 0141-5387 .- 1460-2210. ; 46:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To assess if the dental follicle volume of palatally impacted canines (PICs) affects the relative root position of the adjacent lateral incisors (LIs) and first premolars (FPs).Materials and Methods A retrospective cross-sectional study of 49 patients with unilaterally PICs with dental follicles who had CBCT imaging previously taken. Four orthodontic centers in different countries provided the sample. A mean difference of 5 degrees between the angular measurements (mesiodistal tip, buccolingual inclination, or mesiodistal rotation) of the LI and FP adjacent to the PIC and the controls was considered clinically relevant. A value of 0.05 was set for significance level and a power of 80%. The minimum sample size was determined to be 26 patients. These patients were further assigned to an LI sample (n = 49) and an FP sample (n = 23), dependent on the direct contact of the dental follicle to that adjacent tooth. A manual segmentation technique was used to obtain the volumetric measurements of the dental follicle. Angular measurements of adjacent teeth were then compared to the contralateral nonimpacted side, which acted as the control. A multivariant regression analysis was performed using IBM SPSS software, and statistical significance was set at alpha = 0.05.Results Adequate intra-rater reliability was accomplished. The multivariant regression analysis implied that there is no difference in the mean change in the tip, torque, and rotation of the LI and FP between the impacted and control sides when dental follicle volumes are considered (P = .509 for the LI sample and P = .804 for the FP sample).Limitations CBCT imaging of dental follicle border delimitations, partial volume effect, and scattering are limitations. This is a convenience sample where the FP subsample is small.Conclusion The dental follicle volume of the PICs does not seem to influence the relative position of the adjacent LI and FP mesiodistal tip, buccolingual inclination, and mesiodistal rotation. Early intervention could have been suggested to avoid certain malocclusion traits if significant displacements were demonstrated.
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27.
  • Lee, Dung-Fang, et al. (författare)
  • Regulation of embryonic and induced pluripotency by aurora kinase-p53 signaling.
  • 2012
  • Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Many signals must be integrated to maintain self-renewal and pluripotency in embryonic stem cells (ESCs) and to enable induced pluripotent stem cell (iPSC) reprogramming. However, the exact molecular regulatory mechanisms remain elusive. To unravel the essential internal and external signals required for sustaining the ESC state, we conducted a short hairpin (sh) RNA screen of 104 ESC-associated phosphoregulators. Depletion of one such molecule, aurora kinase A (Aurka), resulted in compromised self-renewal and consequent differentiation. By integrating global gene expression and computational analyses, we discovered that loss of Aurka leads to upregulated p53 activity that triggers ESC differentiation. Specifically, Aurka regulates pluripotency through phosphorylation-mediated inhibition of p53-directed ectodermal and mesodermal gene expression. Phosphorylation of p53 not only impairs p53-induced ESC differentiation but also p53-mediated suppression of iPSC reprogramming. Our studies demonstrate an essential role for Aurka-p53 signaling in the regulation of self-renewal, differentiation, and somatic cell reprogramming.
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28.
  • Macías, Daniel Isaías Burgos, et al. (författare)
  • Asociación entre la presencia de anticuerpos contra Leptospira y lesiones renales en bovinos
  • 2020
  • Ingår i: Revista de Investigaciones Veterinarias del Perú. - : Universidad Nacional Mayor de San Marcos, Vicerectorado de Investigacion. - 1682-3419 .- 1609-9117. ; 31:4
  • Tidskriftsartikel (refereegranskat)abstract
    • El estudio tuvo como objetivo determinar la posible relación entre la presencia de lesiones denominadas «Riñón con Manchas Blancas» (RMB) y la seroprevalencia de Leptospira spp en bovinos sacrificados en el matadero del cantón Manta, provincia Manabí, Ecuador. Se tomaron muestras de sangre a 320 bovinos para detectar anticuerpos contra bacterias del género Leptospira utilizando la técnica de microaglutinación. Asi-mismo, se hizo una revisión macroscópica de los riñones y se tomaron muestras para el análisis histopatológico. La seroprevalencia de Leptospira spp fue de 50.9% y la fre-cuencia de lesiones renales fue de 18.13%. Se encontró la presencia de los ocho serovares evaluados, siendo mayor la frecuencia de los serovares Pomona, Icterohaemorragiae y Bratislava. Los animales serológicamente positivos a Leptospira presentan 40.56 más probabilidad de presentar lesiones específicas asociadas con la enfermedad al momento del sacrificio (p<0.00001; OR=40.56; IC 95%= 9.86-169.79). Se determinó asociación signi-ficativa entre la presencia de lesiones renales con los serovares Icterohaemorragiae, Canicola, Hardjo y Wolffi. No se encontró asociación entre la presencia de lesiones con el sexo de los animales ni con el cantón de procedencia. Se concluye que existe relación entre la seroprevalencia a Leptospira spp y la presencia de lesiones renales (RMB).
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29.
  • Olson, Nathan D., et al. (författare)
  • precisionFDA Truth Challenge V2: Calling variants from short- and long-reads in difficult-to-map regions
  • 2020
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • The precisionFDA Truth Challenge V2 aimed to assess the state-of-the-art of variant calling in difficult-to-map regions and the Major Histocompatibility Complex (MHC). Starting with FASTQ files, 20 challenge participants applied their variant calling pipelines and submitted 64 variant callsets for one or more sequencing technologies (~35X Illumina, ~35X PacBio HiFi, and ~50X Oxford Nanopore Technologies). Submissions were evaluated following best practices for benchmarking small variants with the new GIAB benchmark sets and genome stratifications. Challenge submissions included a number of innovative methods for all three technologies, with graph-based and machine-learning methods scoring best for short-read and long-read datasets, respectively. New methods out-performed the 2016 Truth Challenge winners, and new machine-learning approaches combining multiple sequencing technologies performed particularly well. Recent developments in sequencing and variant calling have enabled benchmarking variants in challenging genomic regions, paving the way for the identification of previously unknown clinically relevant variants.
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30.
  • Olson, Nathan D., et al. (författare)
  • PrecisionFDA Truth Challenge V2: Calling variants from short and long reads in difficult-to-map regions
  • 2022
  • Ingår i: Cell Genomics. - : Elsevier BV. - 2666-979X. ; 2:5, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • The precisionFDA Truth Challenge V2 aimed to assess the state of the art of variant calling in challenging genomic regions. Starting with FASTQs, 20 challenge participants applied their variant-calling pipelines and submitted 64 variant call sets for one or more sequencing technologies (Illumina, PacBio HiFi, and Oxford Nanopore Technologies). Submissions were evaluated following best practices for benchmarking small variants with updated Genome in a Bottle benchmark sets and genome stratifications. Challenge submissions included numerous innovative methods, with graph-based and machine learning methods scoring best for short-read and long-read datasets, respectively. With machine learning approaches, combining multiple sequencing technologies performed particularly well. Recent developments in sequencing and variant calling have enabled benchmarking variants in challenging genomic regions, paving the way for the identification of previously unknown clinically relevant variants.
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31.
  • Pastor, Ada, et al. (författare)
  • Local and regional drivers of headwater streams metabolism : insights from the first AIL collaborative project
  • 2017
  • Ingår i: LIMNETICA. - : Asociacion Iberica de Limnologia. - 0213-8409 .- 1989-1806. ; 36:1, s. 67-85
  • Tidskriftsartikel (refereegranskat)abstract
    • Streams play a key role in the global biogeochemical cycles, processing material from adjacent terrestrial systems and transporting it downstream. However, the drivers of stream metabolism, especially those acting at broad spatial scales, are still not well understood. Moreover, stream metabolism can be affected by hydrological changes associated with seasonality, and thus, assessing the temporality of metabolic rates is a key question to understand stream function. This study aims to analyse the geographical and temporal patterns in stream metabolism and to identify the main drivers regulating the whole ecosystem metabolic rates at local and regional scales. Using a coordinated distributed experiment, we studied ten headwaters streams located across five European ecoregions during summer and fall 2014. We characterized the magnitude and variability of gross primary production (GPP) and ecosystem respiration (ER) with the open-channel method. Moreover, we examined several climatic, geographical, hydrological, morphological, and physicochemical variables that can potentially control stream metabolic rates. Daily rates of stream metabolism varied considerately across streams, with GPP and ER ranging from 0.06 to 4.33 g O-2 m(-2) d(-1) and from 0.72 to 14.20 g O-2 m(-2) d(-1), respectively. All streams were highly heterotrophic (P/R < 1), except the southernmost one. We found that the drier climates tended to have the highest GPP, while humid regions presented the highest ER. Between the sampling periods no statistical differences were found. Partial-least squares models (PLS) explained similar to 80% of the variance in GPP and ER rates across headwater streams and included both local and regional variables. Rates of GPP varied primarily in response to the local variables, such as streambed substrate and stream water temperature. In contrast, regional variables, such as the mean annual temperature or the land use of the catchment, had more relevance to explain ER. Overall, our results highlight that stream metabolism depends on both local and regional drivers and show the positive experience of a young network of researchers to assess scientific challenges across large-scale geographic areas.
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32.
  • Perez Ruano, Miguel, et al. (författare)
  • Seroprevalence and risk factors of bovine leptospirosis in the province of Manabí, Ecuador
  • 2020
  • Ingår i: Comparative Immunology, Microbiology & Infectious Diseases. - : Elsevier. - 0147-9571 .- 1878-1667. ; 72
  • Tidskriftsartikel (refereegranskat)abstract
    • Leptospirosis is a zoonotic disease with worldwide distribution. The disease affects dairy and beef cattle, causing infertility, abortion, and reduced milk yield. A cross-sectional study was conducted to determine the seroprevalence of leptospirosis in cattle and the associated risk factors in the province of Manabi, Ecuador. Serum samples from 749 animals from 55 cattle herds were analyzed using the microscopic agglutination test (MAT). Animals were considered positive when titers were >= 1:100. The association between the potential risk factors and the positive Leptospira result was modeled at both animal and herd level using a generalized linear model with a binomial distribution and logarithmic link. The seroprevalence was 56.21% at the individual level and 98.18% at the herd level. The most prevalent serovars were Pomona (28.57%) and Icterohaemorragiae (22.30%). At the animal level, only the age was associated with leptospirosis seropositivity. Seroprevalence in animals over three years of age was 1.197 (95% confidence intervals (CI), 1.032 - 1.390), higher compared to animals up to three years old. The seroprevalence of Leptospira spp. was higher in farms with no veterinary assistance (PR =1.209; 95%CI 1.053 - 1.388) and without a vaccination program against Leptospira (PR =1.399; 95%CI 1.09 1.794). In addition, herds from Junin canton had a significantly higher seroprevalence of Leptospira spp (PR =1.548; 95%CI 1.213 1.977) compared to the Bolivar canton, which had the lowest seroprevalence. In conclusion, more than half of the animals were positive to Leptospiraspp, and almost all herds had at least one positive animal. Furthermore, veterinary assistance and vaccination of cattle must be considered as essential aspects of the disease control program.
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33.
  • Peripato, Vinicius, et al. (författare)
  • More than 10,000 pre-Columbian earthworks are still hidden throughout Amazonia
  • 2023
  • Ingår i: Science (New York, N.Y.). - 1095-9203. ; 382:6666, s. 103-109
  • Tidskriftsartikel (refereegranskat)abstract
    • Indigenous societies are known to have occupied the Amazon basin for more than 12,000 years, but the scale of their influence on Amazonian forests remains uncertain. We report the discovery, using LIDAR (light detection and ranging) information from across the basin, of 24 previously undetected pre-Columbian earthworks beneath the forest canopy. Modeled distribution and abundance of large-scale archaeological sites across Amazonia suggest that between 10,272 and 23,648 sites remain to be discovered and that most will be found in the southwest. We also identified 53 domesticated tree species significantly associated with earthwork occurrence probability, likely suggesting past management practices. Closed-canopy forests across Amazonia are likely to contain thousands of undiscovered archaeological sites around which pre-Columbian societies actively modified forests, a discovery that opens opportunities for better understanding the magnitude of ancient human influence on Amazonia and its current state.
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34.
  • Petzold, Axel, et al. (författare)
  • Diagnosis and classification of optic neuritis
  • 2022
  • Ingår i: Lancet Neurology. - : ELSEVIER SCIENCE INC. - 1474-4422 .- 1474-4465. ; 21:12, s. 1120-1134
  • Forskningsöversikt (refereegranskat)abstract
    • There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.
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35.
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36.
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37.
  • Strophauer, Emily, et al. (författare)
  • The clinical presentation of major depressive disorder in youth with co-occurring obsessive-compulsive disorder
  • 2024
  • Ingår i: Journal of Affective Disorders. - 0165-0327. ; 349, s. 349-357
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundMajor depressive disorder (MDD) is common in youth and among the most frequent comorbid disorders in pediatric obsessive-compulsive disorder (OCD), but it is unclear whether the presence of OCD affects the symptom presentation of MDD in youth.MethodsA sample of youth with OCD and MDD (n = 124) and a sample of youth with MDD but no OCD (n = 673) completed the Patient Health Questionnaire for Adolescents (PHQ-A). The overall and symptom-level presentation of MDD were examined using group comparisons and network analysis.ResultsYouth with MDD and OCD, compared to those with MDD and no OCD, had more severe MDD (Cohen's d = 0.39) and more reported moderate to severe depression (75 % vs 61 %). When accounting for demographic variables and the overall severity of MDD, those with comorbid OCD reported lower levels of anhedonia and more severe difficulties with psychomotor retardation/agitation. No significant differences in the interconnections among symptoms emerged.LimitationsData were cross-sectional and self-reported, gold standard diagnostic tools were not used to assess OCD, and the sample size for the group with MDD and OCD was relatively small yielding low statistical power for network analysis.ConclusionsYouth with MDD and OCD have more severe MDD than those with MDD and no OCD and they experience more psychomotor issues and less anhedonia, which may relate to the behavioral activation characteristic of OCD.KeywordsOCDChildrenAdolescentsDepressionMajor depressive disorderComorbidity
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38.
  • Vega, Génesis, et al. (författare)
  • Normal calcium-activated anion secretion in a mouse selectively lacking TMEM16A in intestinal epithelium
  • 2019
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Calcium-activated anion secretion is expected to ameliorate cystic fibrosis, a genetic disease that carries an anion secretory defect in exocrine tissues. Human patients and animal models of the disease that present a mild intestinal phenotype have been postulated to bear a compensatory calcium-activated anion secretion in the intestine. TMEM16A is calcium-activated anion channel whose presence in the intestinal epithelium is contradictory. We aim to test the functional expression of TMEM16A using animal models with Cftr and/or Tmem16a intestinal silencing. Expression of TMEM16A was studied in a wild type and intestinal Tmem16a knockout mice by mRNA-seq, mass-spectrometry, q-PCR, Western blotting and immunolocalization. Calcium-activated anion secretion was recorded in the ileum and proximal colon of these animals including intestinal Cftr knockout and double mutants with dual Tmem16a and Cftr intestinal ablation. Mucus homeostasis was studied by immune-analysis of Mucin-2 (Muc2) and survival curves were recorded. Tmem16a transcript was found in intestine. Nevertheless, protein was barely detected in colon samples. Electrophysiological measurements demonstrated that the intestinal deletion of Tmem16a did not change calcium-activated anion secretion induced by carbachol or ATP in ileum and proximal colon. Muc2 architecture was not altered by Tmem16a silencing as was observed when Cftr was deleted from mouse intestine. Tmem16a silencing neither affected animal survival nor modified the lethality observed in the intestinal Cftr-null mouse. Our results demonstrate that TMEM16A function in the murine intestine is not related to electrogenic calcium-activated anion transport and does not affect mucus homeostasis and survival of animals.
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39.
  • Wuestefeld, Anika, et al. (författare)
  • Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories
  • Ingår i: Hippocampus. - 1050-9631.
  • Tidskriftsartikel (refereegranskat)abstract
    • The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the entorhinal and parahippocampal cortices as well as Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 μm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized slices spaced 5 mm apart (pixel size 0.4 μm at 20× magnification). Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while the definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists' agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed less saliently. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed neuroimaging research on the human MTL cortex.
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40.
  • Zanne, Amy E, et al. (författare)
  • Fungal functional ecology: bringing a trait-based approach to plant-associated fungi.
  • 2020
  • Ingår i: Biological reviews of the Cambridge Philosophical Society. - : Wiley. - 1469-185X .- 1464-7931. ; 95:2, s. 409-433
  • Tidskriftsartikel (refereegranskat)abstract
    • Fungi play many essential roles in ecosystems. They facilitate plant access to nutrients and water, serve as decay agents that cycle carbon and nutrients through the soil, water and atmosphere, and are major regulators of macro-organismal populations. Although technological advances are improving the detection and identification of fungi, there still exist key gaps in our ecological knowledge of this kingdom, especially related to function. Trait-based approaches have been instrumental in strengthening our understanding of plant functional ecology and, as such, provide excellent models for deepening our understanding of fungal functional ecology in ways that complement insights gained from traditional and -omics-based techniques. In this review, we synthesize current knowledge of fungal functional ecology, taxonomy and systematics and introduce a novel database of fungal functional traits (FunFun ). FunFun is built to interface with other databases to explore and predict how fungal functional diversity varies by taxonomy, guild, and other evolutionary or ecological grouping variables. To highlight how a quantitative trait-based approach can provide new insights, we describe multiple targeted examples and end by suggesting next steps in the rapidly growing field of fungal functional ecology.
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