Browsing by Subject "ENRICHMENT"

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  • Broman, Elias; Asmala, Eero; Carstensen, Jacob; Pinhassi, Jarone; Dopson, Mark (2019)
    Coastal zones are important transitional areas between the land and sea, where both terrestrial and phytoplankton supplied dissolved organic matter (DOM) are respired or transformed. As climate change is expected to increase river discharge and water temperatures, DOM from both allochthonous and autochthonous sources is projected to increase. As these transformations are largely regulated by bacteria, we analyzed microbial community structure data in relation to a 6-month long time-series dataset of DOM characteristics from Roskilde Fjord and adjacent streams, Denmark. The results showed that the microbial community composition in the outer estuary (closer to the sea) was largely associated with salinity and nutrients, while the inner estuary formed two clusters linked to either nutrients plus allochthonous DOM or autochthonous DOM characteristics. In contrast, the microbial community composition in the streams was found to be mainly associated with allochthonous DOM characteristics. A general pattern across the land-to-sea interface was that Betaproteobacteria were strongly associated with humic-like DOM [operational taxonomic units (OTUs) belonging to family Comamonadaceae], while distinct populations were instead associated with nutrients or abiotic variables such as temperature (Cyanobacteria genus Synechococcus) and salinity (Actinobacteria family Microbacteriaceae). Furthermore, there was a stark shift in the relative abundance of OTUs between stream and marine stations. This indicates that as DOM travels through the land-to-sea interface, different bacterial guilds continuously degrade it.
  • Kivilä, E. Henriikka; Luoto, Tomi P.; Rantala, Marttiina V.; Kiljunen, Mikko; Rautio, Milla; Nevalainen, Liisa (2019)
    Climate warming and consequent greening of subarctic landscapes increase the availability of organic carbon to the detrital food webs in aquatic ecosystems. This may cause important shifts in ecosystem functioning through the functional feeding patterns of benthic organisms that rely differently on climatically altered carbon resources. Twenty-five subarctic lakes in Finnish Lapland across a tree line ecotone were analysed for limnological and optical variables, carbon (delta C-13) and nitrogen (delta N-15) stable isotope (SI) composition of surface sediment organic matter (OM) and fossil Chironomidae (Diptera) remains to examine environmental controls behind chironomid functional feeding group (FFG) structure and their isotopic associations for assessing ecosystem functioning and carbon utilisation. We hypothesise that the chironomid SI signatures reflect increased allochthony with increasing allochthonous input, but the resource use may be altered by the functional characteristics of the assemblage. Multivariate analyses indicated that carbon geochemistry in the sediments (delta C-13, delta N-15, C/N), nutrients, indices of productivity (chlorophyll-a) and lake water optical properties, related to increasing presence of OM, played a key role in defining the chironomid FFG composition and isotopic signatures. Response modelling was used to examine how individual FFGs respond to environmental gradients. They showed divergent responses for OM quantity, dissolved organic carbon and nutrients between feeding strategies, suggesting that detritivores and filter feeders prefer contrasting carbon and nutrient conditions, and may thus hold paleoecological indicator potential to identify changes between different carbon fluxes. Benthic production was the primary carbon source for the chironomid assemblages according to a three-source SI mixing model, whereas pelagic and terrestrial components contributed less. Between-lake variability in source utilisation was high and controlled primarily by allochthonous OM inputs. Combination of biogeochemical modelling and functional classification is useful to widen our understanding of subarctic lake ecosystem functions and responses to climate-driven changes in limnology and catchment characteristics for long-term environmental change assessments and functional paleoecology.
  • Genetics DNA Methylation Consort; NHLBI Trans-Omics Precision Med; McCartney, Daniel L.; Min, Josine L.; Richmond, Rebecca C.; Palviainen, Teemu; Ollikainen, Miina; Kaprio, Jaakko (2021)
    Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
  • Ozkan-Dagliyan, Irem; Diehl, J. Nathaniel; George, Samuel D.; Schaefer, Antje; Papke, Bjoern; Klotz-Noack, Kathleen; Waters, Andrew M.; Goodwin, Craig M.; Gautam, Prson; Pierobon, Mariaelena; Peng, Sen; Gilbert, Thomas S. K.; Lin, Kevin H.; Dagliyan, Onur; Wennerberg, Krister; Petricoin, Emanuel F.; Tran, Nhan L.; Bhagwat, Shripad; Tiu, Ramon; Peng, Sheng-Bin; Herring, Laura E.; Graves, Lee M.; Sers, Christine; Wood, Kris C.; Cox, Adrienne D.; Der, Channing J. (2020)
    We address whether combinations with a pan-RAF inhibitor (RAFi) would be effective in KRAS mutant pancreatic ductal adenocarcinoma (PDAC). Chemical library and CRISPR genetic screens identify combinations causing apoptotic anti-tumor activity. The most potent combination, concurrent inhibition of RAF (RAFi) and ERK (ERKi), is highly synergistic at low doses in cell line, organoid, and rat models of PDAC, whereas each inhibitor alone is only cytostatic. Comprehensive mechanistic signaling studies using reverse phase protein array (RPPA) pathway mapping and RNA sequencing (RNA-seq) show that RAFi/ERKi induced insensitivity to loss of negative feedback and system failures including loss of ERK signaling, FOSL1, and MYC; shutdown of the MYC transcriptome; and induction of mesenchymal-to-epithelial transition. We conclude that low-dose vertical inhibition of the RAF-MEK-ERK cascade is an effective therapeutic strategy for KRAS mutant PDAC.
  • Roth, Florian; El-Khaled, Yusuf C.; Karcher, Denis B.; Rädecker, Nils; Carvalho, Susana; Duarte, Carlos M.; Silva, Luis; Calleja, Maria Ll.; Moran, Xose Anxelu G.; Jones, Burton H.; Voolstra, Christian R.; Wild, Christian (2021)
    Ecosystem services provided by coral reefs may be susceptible to the combined effects of benthic species shifts and anthropogenic nutrient pollution, but related field studies are scarce. We thus investigated in situ how dissolved inorganic nutrient enrichment, maintained for two months, affected community-wide biogeochemical functions of intact coral- and degraded algae-dominated reef patches in the central Red Sea. Results from benthic chamber incubations revealed 87% increased gross productivity and a shift from net calcification to dissolution in algae-dominated communities after nutrient enrichment, but the same processes were unaffected by nutrients in neighboring coral communities. Both community types changed from net dissolved organic nitrogen sinks to sources, but the increase in net release was 56% higher in algae-dominated communities. Nutrient pollution may, thus, amplify the effects of community shifts on key ecosystem services of coral reefs, possibly leading to a loss of structurally complex habitats with carbonate dissolution and altered nutrient recycling.
  • Suzuki, Satoru; Nakanishi, Sayoko; Tamminen, Manu; Yokokawa, Taichi; Sato-Takabe, Yuki; Ohta, Kohei; Chou, Hsin-Yiu; Muziasari, Windi I.; Virta, Marko (2019)
    The use of antibiotics in aquaculture causes selection pressure for antibiotic-resistant bacteria (ARB). Antibiotic resistance genes (ARGs) may persist in ARB and the environment for long time even after stopping drug administration. Here we show monthly differences in the occurrences of genes conferring resistance to sulfonamides (i.e. sul1, sul2, sul3), and tetracyclines (tet(M)) in Japanese aquaculture seawater accompanied by records of drug administration. sul2 was found to persist throughout the year, whereas the occurrences of sul1, sul3, and tet(M) changed month-to-month. sul3 and tet(M) were detected in natural bacterial assemblages in May and July, but not in colony-forming bacteria, thus suggesting that the sul3 was harbored by the non-culturable fraction of the bacterial community. Comparison of results from Taiwanese, Japanese, and Finnish aquaculture waters reveals that the profile of sul genes and tet(M) in Taiwan resembles that in Japan, but is distinct from that in Finland. To our knowledge, this work represents the first report to use the same method to compare the dynamics of sul genes and tet(M) in aquaculture seawater in different countries. (C) 2019 Elsevier B.V. All rights reserved.
  • Chouliaras, Leonidas; Pishva, Ehsan; Haapakoski, Rita; Zsoldos, Eniko; Mahmood, Abda; Filippini, Nicola; Burrage, Joe; Mill, Jonathan; Kivimäki, Mika; Lunnon, Katie; Ebmeier, Klaus P. (2018)
    Aim: The present study investigated the link between peripheral DNA methylation (DNAm), cognitive impairment and brain aging. Methods: We tested the association between blood genome-wide DNAm profiles using the Illumina 450K arrays, cognitive dysfunction and brain MRI measures in selected participants of the Whitehall II imaging sub-study. Results: Eight differentially methylated regions were associated with cognitive impairment. Accelerated aging based on the Hannum epigenetic clock was associated with mean diffusivity and global fractional anisotropy. We also identified modules of co-methylated loci associated with white matter hyperintensities. These co-methylation modules were enriched among pathways relevant to beta-amyloid processing and glutamatergic signaling. Conclusion: Our data support the notion that blood DNAm changes may have utility as a biomarker for cognitive dysfunction and brain aging.
  • Valros, Anna; Barber, Claire (2019)
    Simple Summary Tail biting is a serious behavioural problem in modern pig production which causes both animal welfare challenges and economic losses. The aim of this study was to collect information on the perceptions of farmers on how to best prevent tail biting, and on their attitudes towards tail biting and docking. Further, the aim was to investigate if perceptions are influenced by the specific system of farming, with a focus on different levels of bedding use and different tail docking practices. To achieve the goal, pig producers in the UK were surveyed. The results show that producers rank the importance of preventive measures differently to scientists and other experts. This calls for consideration when communicating with producers, and for further consideration of producer knowledge, which might be based on a more holistic view than that of researchers. The study also shows that the perception of how to best prevent and intervene to avoid tail biting differs between farms of different types, and that these perceptions might be influenced by the farmers' own experiences, which again, might differ between countries and farming systems. Tail biting causes widespread problems both for animal welfare and in the form of economic losses in pig production. This study was performed to better understand the perceptions of farmers on how to best prevent tail biting, and if perceptions are influenced by the specific system of farming, with a focus on different levels of bedding use and docking different proportions of the tail of their pigs. Pig producers in the UK were surveyed on their perceptions of the efficacy of preventive measures and attitudes towards tail biting and docking. In total, 204 responses were included. The results show that producers rank the importance of preventive measures differently to scientists and other experts. This calls for consideration when communicating with producers; and for better integration of knowledge based on practical experiences with scientific results. The study also shows that the perception of how to best avoid tail biting differs between farms of different types, and that these perceptions might be influenced by the farmers ' own experiences-one example being that farms currently using plentiful amounts of bedding also value this more highly as a way to avoid tail biting than those that do not.
  • Mishra, Pashupati P.; Medlar, Alan; Holm, Liisa; Törönen, Petri (2016)
    Background: Competitive gene set analysis is a standard exploratory tool for gene expression data. Permutation-based competitive gene set analysis methods are preferable to parametric ones because the latter make strong statistical assumptions which are not always met. For permutation-based methods, we permute samples, as opposed to genes, as doing so preserves the inter-gene correlation structure. Unfortunately, up until now, sample permutation-based methods have required a minimum of six replicates per sample group. Results: We propose a new permutation-based competitive gene set analysis method for multi-group gene expression data with as few as three replicates per group. The method is based on advanced sample permutation technique that utilizes all groups within a data set for pairwise comparisons. We present a comprehensive evaluation of different permutation techniques, using multiple data sets and contrast the performance of our method, mGSZm, with other state of the art methods. We show that mGSZm is robust, and that, despite only using less than six replicates, we are able to consistently identify a high proportion of the top ranked gene sets from the analysis of a substantially larger data set. Further, we highlight other methods where performance is highly variable and appears dependent on the underlying data set being analyzed. Conclusions: Our results demonstrate that robust gene set analysis of multi-group gene expression data is permissible with as few as three replicates. In doing so, we have extended the applicability of such approaches to resource constrained experiments where additional data generation is prohibitively difficult or expensive. An R package implementing the proposed method and supplementary materials are available from the website http:// ekhidna.biocenter.helsinki.fi/downloads/pashupati/mGSZm.html.
  • Öhman, Tiina; Teppo, Jaakko; Datta, Neeta; Mäkinen, Selina; Varjosalo, Markku; Koistinen, Heikki A. (2021)
    Skeletal muscle insulin resistance is a central defect in the pathogenesis of type 2 diabetes (T2D). Here, we analyzed skeletal muscle proteome in 148 vastus lateralis muscle biopsies obtained from men covering all glucose tolerance phenotypes: normal, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and T2D. Skeletal muscle proteome was analyzed by a sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics technique. Our data indicate a downregulation in several proteins involved inmitochondrial electron transport or respiratory chain complex assembly already in IFG and IGT-muscles, with most profound decreases observed in T2D. Additional phosphoproteomic analysis reveals altered phosphorylation in several signaling pathways in IFG, IGT, and T2D muscles, including those regulating glucose metabolic processes, and the structure of muscle cells. These data reveal several alterations present in skeletalmuscle already in prediabetes and highlight impairedmitochondrial energy metabolism in the trajectory from prediabetes into T2D.
  • Voikar, Vootele; Gaburro, Stefano (2020)
    Animal models of neurodegenerative and neuropsychiatric disorders require extensive behavioral phenotyping. Currently, this presents several caveats and the most important are: (i) rodents are nocturnal animals, but mostly tested during the light period; (ii) the conventional behavioral experiments take into consideration only a snapshot of a rich behavioral repertoire; and (iii) environmental factors, as well as experimenter influence, are often underestimated. Consequently, serious concerns have been expressed regarding the reproducibility of research findings on the one hand, and appropriate welfare of the animals (based on the principle of 3Rs—reduce, refine and replace) on the other hand. To address these problems and improve behavioral phenotyping in general, several solutions have been proposed and developed. Undisturbed, 24/7 home-cage monitoring (HCM) is gaining increased attention and popularity as demonstrating the potential to substitute or complement the conventional phenotyping methods by providing valuable data for identifying the behavioral patterns that may have been missed otherwise. In this review, we will briefly describe the different technologies used for HCM systems. Thereafter, based on our experience, we will focus on two systems, IntelliCage (NewBehavior AG and TSE-systems) and Digital Ventilated Cage (DVC®, Tecniplast)—how they have been developed and applied during recent years. Additionally, we will touch upon the importance of the environmental/experimenter artifacts and propose alternative suggestions for performing phenotyping experiments based on the published evidence. We will discuss how the integration of telemetry systems for deriving certain physiological parameters can help to complement the description of the animal model to offer better translation to human studies. Ultimately, we will discuss how such HCM data can be statistically interpreted and analyzed.
  • Kruse, Thomas; Levisson, Mark; de Vos, Willem M.; Smidt, Hauke (2014)