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Sökning: WFRF:(Nilsson Henrik 1976)

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1.
  • Bidartondo, Martin, et al. (författare)
  • Preserving accuracy in GenBank
  • 2008
  • Ingår i: Science. ; 319:5870
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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2.
  • Einarsdottir, Berglind Osk, 1979, et al. (författare)
  • Melanoma patient-derived xenografts accurately model the disease and develop fast enough to guide treatment decisions.
  • 2014
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 5:20, s. 9609-18
  • Tidskriftsartikel (refereegranskat)abstract
    • The development of novel therapies against melanoma would benefit from individualized tumor models to ensure the rapid and accurate identification of biomarkers of therapy response. Previous studies have suggested that patient-derived xenografts (PDXes) could be useful. However, the utility of PDXes in guiding real-time treatment decisions has only been reported in anecdotal forms. Here tumor biopsies from patients with stage III and IV metastatic malignant melanoma were transplanted into immunocompromised mice to generate PDXes. 23/26 melanoma biopsies generated serially transplantable PDX models, and their histology, mutation status and expression profile resembled their corresponding patient biopsy. The potential treatment for one patient was revealed by an in vitro drug screen and treating PDXes with the MEK inhibitor trametinib. In another patient, the BRAF mutation predicted the response of both the patient and its corresponding PDXes to MAPK-targeted therapy. Importantly, in this unselected group of patients, the time from biopsy for generation of PDXes until death was significantly longer than the time required to reach the treatment phase of the PDXes. Thus, it could be clinically meaningful to use this type of platform for melanoma patients as a pre-selection tool in clinical trials.
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3.
  • Forsberg, Elin, et al. (författare)
  • HER2 CAR-T Cells Eradicate Uveal Melanoma and T-cell Therapy-Resistant Human Melanoma in IL2 Transgenic NOD/SCID IL2 Receptor Knockout Mice
  • 2019
  • Ingår i: Cancer Research. - 0008-5472. ; 79:5, s. 899-904
  • Tidskriftsartikel (refereegranskat)abstract
    • Chimeric antigen receptors (CAR) can transmit signals akin to those from activated T-cell receptors when bound to a cell surface target. CAR-expressing T cells against CD19 can cause curative effects in leukemia and lymphoma and is approved for clinical use. However, no CAR-T therapy is currently approved for use in solid tumors. We hypothesize that the resistance of solid tumors to CAR-T can be overcome by similar means as those used to reactivate tumor-infiltrating T lymphocytes (TIL), for example, by cytokines or immune checkpoint blockade. Here we demonstrate that CAR-T cells directed against HER2 can kill uveal and cutaneous melanoma cells in vitro and in vivo. Curative effects in vivo were only observed in xenografts grown in a NOD/SCID IL2 receptor gamma (NOG) knockout mouse strain transgenic for human IL2. The effect was target-specific, as CRISPR/Cas9-mediated disruption of HER2 in the melanoma cells abrogated the killing effect of the CAR-T cells. The CAR-T cells were also able to kill melanoma cells from patients resistant to adoptive T-cell transfer (ACT) of autologous TILs. Thus, CAR-T therapy represents an option for patients that do not respond to immunotherapy with ACT of TIL or immune checkpoint blockade. In addition, our data highlight the use of IL2 transgenic NOG mice as models to prove efficacy of CAR-T-cell products, possibly even in a personalized manner. Significance: These findings demonstrate that a novel humanized mouse model can help clinical translation of CAR-T cells against uveal and cutaneous melanoma that do not respond to TIL therapy or immune checkpoint blockade.
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4.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • A comprehensive, automatically updated fungal ITS sequence dataset for reference-based chimera control in environmental sequencing efforts
  • 2015
  • Ingår i: Microbes and Environments. - 1342-6311 .- 1347-4405. ; 30:2, s. 145-150
  • Tidskriftsartikel (refereegranskat)abstract
    • The nuclear ribosomal internal transcribed spacer (ITS) region is the most commonly chosen genetic marker for the molecular identification of fungi in environmental sequencing and molecular ecology studies. Several analytical issues complicate such efforts, one of which is the formation of chimeric—artificially joined—DNA sequences during PCR amplification or sequence assembly. Several software tools are currently available for chimera detection, but rely to various degrees on the presence of a chimera-free reference dataset for optimal performance. However, no such dataset is available for use with the fungal ITS region. This study introduces a comprehensive, automatically updated reference dataset for fungal ITS sequences based on the UNITE database for the molecular identification of fungi. This dataset supports chimera detection throughout the fungal kingdom and for full-length ITS sequences as well as partial (ITS1 or ITS2 only) datasets. The performance of the dataset on a large set of artificial chimeras was above 99.5%, and we subsequently used the dataset to remove nearly 1,000 compromised fungal ITS sequences from public circulation. The dataset is available at http://unite.ut.ee/repository.php and is subject to web-based third-party curation.
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5.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • A note on the incidence of reverse complementary fungal ITS sequences in the public sequence databases and a software tool for their detection and reorientation
  • 2011
  • Ingår i: Mycoscience. - : The Mycological Society of Japan. - 1340-3540 .- 1618-2545. ; 52:4, s. 278-282
  • Tidskriftsartikel (refereegranskat)abstract
    • Reverse complementary DNA sequences––sequences that are inadvertently cast backward and in which all purines and pyrimidines are transposed––are not uncommon in sequence databases, where they may introduce noise into sequence-based research. We show that about 1% of the public fungal ITS sequences, the most commonly sequenced genetic marker in mycology, are reverse complementary, and we introduce an open source software solution to automate their detection and reorientation. The MacOSX/Linux/UNIX software operates on public or private datasets of any size, although some 50 base pairs of the 5.8S gene of the ITS region are needed for the analysis.
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6.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • An open source chimera checker for the fungal ITS region
  • 2010
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-0998 .- 1755-098X. ; 10:6, s. 1076-1081
  • Tidskriftsartikel (refereegranskat)abstract
    • The internal transcribed spacer (ITS) region of the nuclear ribosomal repeat unit holds a central position in the pursuit of the taxonomic affiliation of fungi recovered through environmental sampling. Newly generated fungal ITS sequences are typically compared against the International Nucleotide Sequence Databases for a species or genus name using the sequence similarity software suite blast. Such searches are not without complications however, and one of them is the presence of chimeric entries among the query or reference sequences. Chimeras are artificial sequences, generated unintentionally during the polymerase chain reaction step, that feature sequence data from two (or possibly more) distinct species. Available software solutions for chimera control do not readily target the fungal ITS region, but the present study introduces a blast-based open source software package (available at http://www.emerencia.org/chimerachecker.html) to examine newly generated fungal ITS sequences for the presence of potentially chimeric elements in batch mode. We used the software package on a random set of 12 300 environmental fungal ITS sequences in the public sequence databases and found 1.5% of the entries to be chimeric at the ordinal level after manual verification of the results. The proportion of chimeras in the sequence databases can be hypothesized to increase as emerging sequencing technologies drawing from pooled DNA samples are becoming important tools in molecular ecology research.
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7.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Approaching the taxonomic affiliation of unidentified sequences in public databases an example from the mycorrhizal fungi
  • 2005
  • Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 6:178
  • Tidskriftsartikel (refereegranskat)abstract
    • Background During the last few years, DNA sequence analysis has become one of the primary means of taxonomic identification of species, particularly so for species that are minute or otherwise lack distinct, readily obtainable morphological characters. Although the number of sequences available for comparison in public databases such as GenBank increases exponentially, only a minuscule fraction of all organisms have been sequenced, leaving taxon sampling a momentous problem for sequence-based taxonomic identification. When querying GenBank with a set of unidentified sequences, a considerable proportion typically lack fully identified matches, forming an ever-mounting pile of sequences that the researcher will have to monitor manually in the hope that new, clarifying sequences have been submitted by other researchers. To alleviate these concerns, a project to automatically monitor select unidentified sequences in GenBank for taxonomic progress through repeated local BLAST searches was initiated. Mycorrhizal fungi – a field where species identification often is prohibitively complex – and the much used ITS locus were chosen as test bed. Results A Perl script package called emerencia is presented. On a regular basis, it downloads select sequences from GenBank, separates the identified sequences from those insufficiently identified, and performs BLAST searches between these two datasets, storing all results in an SQL database. On the accompanying web-service http://emerencia.math.chalmers.se webcite, users can monitor the taxonomic progress of insufficiently identified sequences over time, either through active searches or by signing up for e-mail notification upon disclosure of better matches. Other search categories, such as listing all insufficiently identified sequences (and their present best fully identified matches) publication-wise, are also available. Discussion The ever-increasing use of DNA sequences for identification purposes largely falls back on the assumption that public sequence databases contain a thorough sampling of taxonomically well-annotated sequences. Taxonomy, held by some to be an old-fashioned trade, has accordingly never been more important. emerencia does not automate the taxonomic process, but it does allow researchers to focus their efforts elsewhere than countless manual BLAST runs and arduous sieving of BLAST hit lists. The emerencia system is available on an open source basis for local installation with any organism and gene group as targets.
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8.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Five simple guidelines for establishing basic authenticity and reliability of newly generated fungal ITS sequences
  • 2012
  • Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 4, s. 37-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Molecular data form an important research tool in most branches of mycology. A non-trivial proportion of the public fungal DNA sequences are, however, compromised in terms of quality and reliability, contributing noise and bias to sequence-borne inferences such as phylogenetic analysis, diversity assessment, and barcoding. In this paper we discuss various aspects and pitfalls of sequence quality assessment. Based on our observations, we provide a set of guidelines to assist in manual quality management of newly generated, near-full-length (Sanger-derived) fungal ITS sequences and to some extent also sequences of shorter read lengths, other genes or markers, and groups of organisms. The guidelines are intentionally non-technical and do not require substantial bioinformatics skills or significant computational power. Despite their simple nature, we feel they would have caught the vast majority of the severely compromised ITS sequences in the public corpus. Our guidelines are nevertheless not infallible, and common sense and intuition remain important elements in the pursuit of compromised sequence data. The guidelines focus on basic sequence authenticity and reliability of the newly generated sequences, and the user may want to consider additional resources and steps to accomplish the best possible quality control. A discussion on the technical resources for further sequence quality management is therefore provided in the supplementary material.
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9.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Intraspecific ITS Variability in the Kingdom Fungi as Expressed in the International Sequence Databases and Its Implications for Molecular Species Identification
  • 2008
  • Ingår i: Evolutionary Bioinformatics. - 1176-9343. ; 2008:4, s. 193-201
  • Tidskriftsartikel (refereegranskat)abstract
    • The internal transcribed spacer (ITS) region of the nuclear ribosomal repeat unit is the most popular locus for species identification and subgeneric phylogenetic inference in sequencebased mycological research. The region is known to show certain variability even within species, although its intraspecific variability is often held to be limited and clearly separated from interspecific variability. The existence of such a divide between intra and interspecific variability is implicitly assumed by automated approaches to species identification, but whether intraspecific variability indeed is negligible within the fungal kingdom remains contentious. The present study estimates the intraspecific ITS variability in all fungi presently available to the mycological community through the international sequence databases. Substantial differences were found within the kingdom, and the results are not easily correlated to the taxonomic affiliation or nutritional mode of the taxa considered. No single unifying yet stringent upper limit for intraspecific variability, such as the canonical 3 % threshold, appears to be applicable with the desired outcome throughout the fungi. Our results caution against simplified approaches to automated ITSbased species delimitation and reiterate the need for taxonomic expertise in the translation of sequence data into species names.
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10.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Taxonomic reliability of DNA sequences in public sequence databases: A fungal perspective
  • 2006
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 1:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background DNA sequences are increasingly seen as one of the primary information sources for species identification in many organism groups. Such approaches, popularly known as barcoding, are underpinned by the assumption that the reference databases used for comparison are sufficiently complete and feature correctly and informatively annotated entries. Methodology/Principal Findings The present study uses a large set of fungal DNA sequences from the inclusive International Nucleotide Sequence Database to show that the taxon sampling of fungi is far from complete, that about 20% of the entries may be incorrectly identified to species level, and that the majority of entries lack descriptive and up-to-date annotations. Conclusions The problems with taxonomic reliability and insufficient annotations in public DNA repositories form a tangible obstacle to sequence-based species identification, and it is manifest that the greatest challenges to biological barcoding will be of taxonomical, rather than technical, nature.
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11.
  • Tedersoo, Leho, et al. (författare)
  • Tidying up international nucleotide sequence databases: ecological, geographical and sequence quality annotation of ITS sequences of mycorrhizal fungi
  • 2011
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Sequence analysis of the ribosomal RNA operon, particularly the internal transcribed spacer (ITS) region, provides a powerful tool for identification of mycorrhizal fungi. The sequence data deposited in the International Nucleotide Sequence Databases (INSD) are, however, unfiltered for quality and are often poorly annotated with metadata. To detect chimeric and low-quality sequences and assign the ectomycorrhizal fungi to phylogenetic lineages, fungal ITS sequences were downloaded from INSD, aligned within family-level groups, and examined through phylogenetic analyses and BLAST searches. By combining the fungal sequence database UNITE and the annotation and search tool PlutoF, we also added metadata from the literature to these accessions. Altogether 35,632 sequences belonged to mycorrhizal fungi or originated from ericoid and orchid mycorrhizal roots. Of these sequences, 677 were considered chimeric and 2,174 of low read quality. Information detailing country of collection, geographical coordinates, interacting taxon and isolation source were supplemented to cover 78.0%, 33.0%, 41.7% and 96.4% of the sequences, respectively. These annotated sequences are publicly available via UNITE (http://unite.ut.ee/) for downstream biogeographic, ecological and taxonomic analyses. In European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena/), the annotated sequences have a special link-out to UNITE. We intend to expand the data annotation to additional genes and all taxonomic groups and functional guilds of fungi.
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12.
  • Abarenkov, Kessy, et al. (författare)
  • Annotating public fungal ITS sequences from the built environment according to the MIxS-Built Environment standard – a report from a May 23-24, 2016 workshop (Gothenburg, Sweden)
  • 2016
  • Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 16, s. 1-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent molecular studies have identified substantial fungal diversity in indoor environments. Fungi and fungal particles have been linked to a range of potentially unwanted effects in the built environment, including asthma, decay of building materials, and food spoilage. The study of the built mycobiome is hampered by a number of constraints, one of which is the poor state of the metadata annotation of fungal DNA sequences from the built environment in public databases. In order to enable precise interrogation of such data – for example, “retrieve all fungal sequences recovered from bathrooms” – a workshop was organized at the University of Gothenburg (May 23-24, 2016) to annotate public fungal barcode (ITS) sequences according to the MIxS-Built Environment annotation standard (http://gensc.org/mixs/). The 36 participants assembled a total of 45,488 data points from the published literature, including the addition of 8,430 instances of countries of collection from a total of 83 countries, 5,801 instances of building types, and 3,876 instances of surface-air contaminants. The results were implemented in the UNITE database for molecular identification of fungi (http://unite.ut.ee) and were shared with other online resources. Data obtained from human/animal pathogenic fungi will furthermore be verified on culture based metadata for subsequent inclusion in the ISHAM-ITS database (http://its.mycologylab.org).
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13.
  • Abarenkov, Kessy, et al. (författare)
  • PlutoF—a web based workbench for ecological and taxonomic research, with an online implementation for fungal ITS sequences
  • 2010
  • Ingår i: Evolutionary Bioinformatics. - 1176-9343. ; 6, s. 189-196
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA sequences accumulating in the International Nucleotide Sequence Databases (INSD) form a rich source of information for taxonomic and ecological meta-analyses. However, these databases include many erroneous entries, and the data itself is poorly annotated with metadata, making it difficult to target and extract entries of interest with any degree of precision. Here we describe the web-based workbench PlutoF, which is designed to bridge the gap between the needs of contemporary research in biology and the existing software resources and databases. Built on a relational database, PlutoF allows remote-access rapid submission, retrieval, and analysis of study, specimen, and sequence data in INSD as well as for private datasets though web-based thin clients. In contrast to INSD, PlutoF supports internationally standardized terminology to allow very specific annotation and linking of interacting specimens and species. The sequence analysis module is optimized for identification and analysis of environmental ITS sequences of fungi, but it can be modified to operate on any genetic marker and group of organisms. The workbench is available at http://plutof.ut.ee.
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14.
  • Abarenkov, Kessy, et al. (författare)
  • The UNITE database for molecular identification and taxonomic communication of fungi and other eukaryotes: sequences, taxa and classifications reconsidered
  • 2024
  • Ingår i: Nucleic Acids Research. - 0305-1048 .- 1362-4962. ; 52:D1, s. D791-D797
  • Tidskriftsartikel (refereegranskat)abstract
    • UNITE (https://unite.ut.ee) is a web-based database and sequence management environment for molecular identification of eukaryotes. It targets the nuclear ribosomal internal transcribed spacer (ITS) region and offers nearly 10 million such sequences for reference. These are clustered into similar to 2.4M species hypotheses (SHs), each assigned a unique digital object identifier (DOI) to promote unambiguous referencing across studies. UNITE users have contributed over 600 000 third-party sequence annotations, which are shared with a range of databases and other community resources. Recent improvements facilitate the detection of cross-kingdom biological associations and the integration of undescribed groups of organisms into everyday biological pursuits. Serving as a digital twin for eukaryotic biodiversity and communities worldwide, the latest release of UNITE offers improved avenues for biodiversity discovery, precise taxonomic communication and integration of biological knowledge across platforms. Graphical Abstract
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15.
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16.
  • Antonelli, Alexandre, 1978, et al. (författare)
  • SUPERSMART: ecology and evolution in the era of big data
  • 2014
  • Ingår i: PeerJ PrePrints. - : PeerJ. - 2167-9843.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Rapidly growing biological data volumes – including molecular sequences, species traits, geographic occurrences, specimen collections, and fossil records – hold an unprecedented, yet largely unexplored potential to reveal how ecological and evolutionary processes generate and maintain biodiversity. Most biodiversity studies integrating ecological data and evolutionary history use an idiosyncratic step-by-step approach for the reconstruction of time-calibrated phylogenies in light of ecological and evolutionary scenarios. Here we introduce a conceptual framework, termed SUPERSMART (Self-Updating Platform for Estimating Rates of Speciation and Migration, Ages, and Relationships of Taxa), and provide a proof of concept for dealing with the moving targets of biodiversity research. This framework reconstructs dated phylogenies based on the assembly of molecular datasets and collects pertinent data on ecology, distribution, and fossils of the focal clade. The data handled for each step are continuously updated as databases accumulate new records. We exemplify the practice of our method by presenting comprehensive phylogenetic and dating analyses for the orders Primates and the Gentianales. We believe that this emerging framework will provide an invaluable tool for a wide range of hypothesis-driven research questions in ecology and evolution.
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17.
  • Bengtsson-Palme, Johan, 1985, et al. (författare)
  • Improved software detection and extraction of ITS1 and ITS2 from ribosomal ITS sequences of fungi and other eukaryotes for analysis of environmental sequencing data
  • 2013
  • Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 4:10, s. 914-919
  • Tidskriftsartikel (refereegranskat)abstract
    • The nuclear ribosomal internal transcribed spacer (ITS) region is the primary choice for molecular identification of fungi. Its two highly variable spacers (ITS1 and ITS2) are usually species specific, whereas the intercalary 5.8S gene is highly conserved. For sequence clustering and blast searches, it is often advantageous to rely on either one of the variable spacers but not the conserved 5.8S gene. To identify and extract ITS1 and ITS2 from large taxonomic and environmental data sets is, however, often difficult, and many ITS sequences are incorrectly delimited in the public sequence databases. We introduce ITSx, a Perl-based software tool to extract ITS1, 5.8S and ITS2 – as well as full-length ITS sequences – from both Sanger and high-throughput sequencing data sets. ITSx uses hidden Markov models computed from large alignments of a total of 20 groups of eukaryotes, including fungi, metazoans and plants, and the sequence extraction is based on the predicted positions of the ribosomal genes in the sequences. ITSx has a very high proportion of true-positive extractions and a low proportion of false-positive extractions. Additionally, process parallelization permits expedient analyses of very large data sets, such as a one million sequence amplicon pyrosequencing data set. ITSx is rich in features and written to be easily incorporated into automated sequence analysis pipelines. ITSx paves the way for more sensitive blast searches and sequence clustering operations for the ITS region in eukaryotes. The software also permits elimination of non-ITS sequences from any data set. This is particularly useful for amplicon-based next-generation sequencing data sets, where insidious non-target sequences are often found among the target sequences. Such non-target sequences are difficult to find by other means and would contribute noise to diversity estimates if left in the data set.
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18.
  • Einarsdottir, Berglind Osk, 1979, et al. (författare)
  • A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
  • 2018
  • Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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19.
  • Eriksson, Martin, 1970, et al. (författare)
  • Triclosan changes community composition and selects for specific bacterial taxa in marine periphyton biofilms in low nanomolar concentrations
  • 2020
  • Ingår i: Ecotoxicology. - : Springer Science and Business Media LLC. - 0963-9292 .- 1573-3017. ; 29:7, s. 1083-1094
  • Tidskriftsartikel (refereegranskat)abstract
    • The antibacterial agent Triclosan (TCS) is a ubiquitous environmental contaminant due to its widespread use. Sensitivity to TCS varies substantially among eu- and pro-karyotic species and its risk for the marine environment remains to be better elucidated. In particular, the effects that TCS causes on marine microbial communities are largely unknown. In this study we therefore used 16S amplicon rDNA sequencing to investigate TCS effects on the bacterial composition in marine periphyton communities that developed under long-term exposure to different TCS concentrations. Exposure to TCS resulted in clear changes in bacterial composition already at concentrations of 1 to 3.16 nM. We conclude that TCS affects the structure of the bacterial part of periphyton communities at concentrations that actually occur in the marine environment. Sensitive taxa, whose abundance decreased significantly with increasing TCS concentrations, include the Rhodobiaceae and Rhodobacteraceae families of Alphaproteobacteria, and unidentified members of the Candidate division Parcubacteria. Tolerant taxa, whose abundance increased significantly with higher TCS concentrations, include the families Erythrobacteraceae (Alphaproteobacteria), Flavobacteriaceae (Bacteroidetes), Bdellovibrionaceae (Deltaproteobacteria), several families of Gammaproteobacteria, and members of the Candidate phylum Gracilibacteria. Our results demonstrate the variability of TCS sensitivity among bacteria, and that TCS can change marine bacterial composition at concentrations that have been detected in the marine environment.
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20.
  • Forsberg, Elin, et al. (författare)
  • Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs
  • 2023
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Simple Summary CAR-T cells are immune cells equipped with a claw that enable them to bind cancer cells. Usually, CAR-T cells are made using immune cells from blood. Here, we tested the hypothesis that also immune cells that reside in the tumor, so called tumor-infiltrating lymphocytes, can also be modified to carry the claw. This may mean that these cells, called CAR-TILs, will be able to attack cancer cells in two ways, using the claw or binding using its normal protein on the cell surface, the so-called T cell receptor. We show that CAR-TILs can be generated, and that they can kill melanoma cells in cell culture and in mice. Finally, to prepare for clinical trials, we also assess if CAR-TILs can be safe in a human cancer patient-like model, a companion dog suffering from cancer. Our data suggest that CAR-TILs may be a way to treat patients with melanoma but human clinical trials are needed. Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma.
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21.
  • Gómez-Martínez, Daniela, et al. (författare)
  • Phenotypic and transcriptomic acclimation of the green microalga Raphidocelis subcapitata to high environmental levels of the herbicide diflufenican
  • 2023
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 875
  • Tidskriftsartikel (refereegranskat)abstract
    • Herbicide pollution poses a worldwide threat to plants and freshwater ecosystems. However, the understanding of how organisms develop tolerance to these chemicals and the associated trade-off expenses are largely unknown. This study aims to investigate the physiological and transcriptional mechanisms underlying the acclimation of the green microalgal model species Raphidocelis subcapitata (Selenastraceae) towards the herbicide diflufenican, and the fitness costs associated with tolerance development. Algae were exposed for 12 weeks (corresponding to 100 generations) to diflufenican at the two environmental concentrations 10 and 310 ng/L. The monitoring of growth, pigment composition, and photosynthetic performance throughout the experiment revealed an initial dose-dependent stress phase (week 1) with an EC50 of 397 ng/L, followed by a time-dependent recovery phase during weeks 2 to 4. After week 4, R. subcapitata was acclimated to diflufenican exposure with a similar growth rate, content of carotenoids, and photosynthetic performance as the unexposed control algae. This acclimation state of the algae was explored in terms of tolerance acquisition, changes in the fatty acids composition, diflufenican removal rate, cell size, and changes in mRNA gene expression profile, revealing potential fitness costs associated with acclimation, such as up-regulation of genes related to cell division, structure, morphology, and reduction of cell size. Overall, this study demonstrates that R. subcapitata can quickly acclimate to environmental but toxic levels of diflufenican; however, the acclimation is associated with trade-off expenses that result in smaller cell size.
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22.
  • Hallenberg, Nils, 1947, et al. (författare)
  • Pseudolagarobasidium (Basidiomycota): on the reinstatement of a genus of parasitic, saprophytic, and endophytic resupinate fungi
  • 2008
  • Ingår i: Botany. - 1916-2804. ; 86:11, s. 1319-1325
  • Tidskriftsartikel (refereegranskat)abstract
    • The small resupinate genus Pseudolagarobasidium (Polyporales, Basidiomycota) presently comprises less than five species, all of which were described from tropical to subtropical regions, and two of which are root parasites on leguminous trees. The genus has recently been synonymized with Radulodon on morphological grounds, and the present study evaluates this proposal in a molecular context. Pseudolagarobasidium was found to constitute a well supported, monophyletic group excluding Radulodon and this synonymy is rejected. The ecological range of the genus spans saprotrophy to parasitism, and this study presents evidence that at least one lineage in Pseudolagarobasidium is endophytic in the cacao tree (Theobroma cacao L.). Key words: Polyporales, Radulodon, phylogeny, plant interactions. Résumé: Le Pseudolagarobasidium (Polyporales, Basidiomycota) constitue un genre de petits champignons résupinés qui comporte actuellement cinq espèces, toutes décrites à partir de régions tropicales ou subtropicales, incluant deux espèces parasites des racines d'arbres de la famille des légumineuses. On en a récemment établi la synonymie avec le genre Radulodon sur la base morphologique, mais les auteurs utilisent ici l'approche moléculaire. On constate que le genre Pseudolagarobasidium constitue un groupe monophylétique robuste excluant les Radulodon ce qui conduit au rejet de cette synonymie. L'amplitude écologique du genre va du saprophytisme au parasitisme, et on présente des preuves qu'au moins une lignée est un endophyte du cacaoyer (Theobroma cacao L.). Mots-clés : Polyporales, Radulon, phylogénie, interactions végétales.
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23.
  • Hibbett, David S., et al. (författare)
  • Agaricomycetes
  • 2014
  • Ingår i: The Mycota. - Berlin : Springer. - 9783642553172 ; , s. 373-429
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Agaricomycetes includes ca. 21,000 described species of mushroom-forming fungi that function as decayers, pathogens, and mutualists in both terrestrial and aquatic habitats. The morphological diversity of Agaricomycete fruiting bodies is unparalleled in any other group of fungi, ranging from simple corticioid forms to complex, developmentally integrated forms (e.g., stinkhorns). In recent years, understanding of the phylogenetic relationships and biodiversity of Agaricomycetes has advanced dramatically, through a combination of polymerase chain reaction-based multilocus phylogenetics, phylogenomics, and molecular environmental surveys. Agaricomycetes is strongly supported as a clade and includes several groups formerly regarded as Heterobasidiomycetes, namely the Auriculariales, Sebacinales, and certain Cantharellales (Tulasnellaceae and Ceratobasidiaceae). The Agaricomycetes can be divided into 20 mutually exclusive clades that have been treated as orders. This chapter presents an overview of the phylogenetic diversity of Agaricomycetes, emphasizing recent molecular phylogenetic studies.
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24.
  • Hyde, Kevin D., et al. (författare)
  • Incorporating molecular data in fungal systematics: a guide for aspiring researchers
  • 2013
  • Ingår i: Current Research in Environmental and Applied Mycology. - : Mushroom Research Foundation. - 2229-2225. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The last twenty years have witnessed molecular data emerge as a primary research instrument in most branches of mycology. Fungal systematics, taxonomy, and ecology have all seen tremendous progress and have undergone rapid, far-reaching changes as disciplines in the wake of continual improvement in DNA sequencing technology. A taxonomic study that draws from molecular data involves a long series of steps, ranging from taxon sampling through the various laboratory procedures and data analysis to the publication process. All steps are important and influence the results and the way they are perceived by the scientific community. The present paper provides a reflective overview of all major steps in such a project with the purpose to assist research students about to begin their first study using DNA-based methods. We also take the opportunity to discuss the role of taxonomy in biology and the life sciences in general in the light of molecular data. While the best way to learn molecular methods is to work side by side with someone experienced, we hope that the present paper will serve to lower the learning threshold for the reader.
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25.
  • Jespersen, Henrik, et al. (författare)
  • Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model.
  • 2017
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Immune checkpoint inhibitors and adoptive cell transfer (ACT) of autologous tumor-infiltrating T cells have shown durable responses in patients with melanoma. To study ACT and immunotherapies in a humanized model, we have developed PDXv2.0 -a melanoma PDX model where tumor cells and tumor-infiltrating T cells from the same patient are transplanted sequentially in non-obese diabetic/severe combined immune-deficient/common gamma chain (NOG/NSG) knockout mouse. Key to T-cell survival/effect in this model is the continuous presence of interleukin-2 (IL-2). Tumors that grow in PDXv2.0 are eradicated if the autologous tumor cells and T cells come from a patient that exhibited an objective response to ACT in the clinic. However, T cells from patients that are non-responders to ACT cannot kill tumor cells in PDXv2.0. Taken together, PDXv2.0 provides the potential framework to further model genetically diverse human cancers for assessing the efficacy of immunotherapies as well as combination therapies.Combining different types of immune therapies might benefit certain patients. Here, the authors develop an autologous immune-humanized melanoma mouse model that allows the preclinical assessment of cancer cell-T cell interactions from each individual patient and the benefits of immunotherapies combinations.
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26.
  • Jespersen, Henrik, et al. (författare)
  • Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): protocol for a multicenter phase II open label study.
  • 2019
  • Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in metastatic uveal melanoma. Thus, metastatic uveal melanoma remains a disease with an urgent unmet medical need. Reports of treatment with immune checkpoint inhibitors have thus far been disappointing. Based on animal experiments, it is reasonable to hypothesize that the effect of immunotherapy may be augmented by epigenetic therapy. Proposed mechanisms include enhanced expression of HLA class I and cancer antigens on cancer cells, as well as suppression of myeloid suppressor cells.The PEMDAC study is a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD1 inhibitor pembrolizumab and the class I HDAC inhibitor entinostat in adult patients with metastatic uveal melanoma. Primary endpoint is objective response rate. Eligible patients have histologically confirmed metastatic uveal melanoma, ECOG performance status 0-1, measurable disease as per RECIST 1.1 and may have received any number of prior therapies, with the exception of anticancer immunotherapy. Twenty nine patients will be enrolled. Patients receive pembrolizumab 200mg intravenously every third week in combination with entinostat 5mg orally once weekly. Treatment will continue until progression of disease or intolerable toxicity or for a maximum of 24months.The PEMDAC study is the first trial to assess whether the addition of an HDAC inhibitor to anti-PD1 therapy can yield objective anti-tumoral responses in metastatic UM.ClinicalTrials.gov registration number: NCT02697630 . (Registered 3 March 2016). EudraCT registration number: 2016-002114-50.
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27.
  • Karlsson, Joakim, et al. (författare)
  • Molecular profiling of driver events in metastatic uveal melanoma
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has ahigh mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genesassociated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease. © 2020, The Author(s).
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28.
  • Kõljalg, U., et al. (författare)
  • The taxon hypothesis paradigm—On the unambiguous detection and communication of taxa
  • 2020
  • Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 8:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we describe the taxon hypothesis (TH) paradigm, which covers the construction, identification, and communication of taxa as datasets. Defining taxa as datasets of individuals and their traits will make taxon identification and most importantly communication of taxa precise and reproducible. This will allow datasets with standardized and atomized traits to be used digitally in identification pipelines and communicated through persistent identifiers. Such datasets are particularly useful in the context of formally undescribed or even physically undiscovered species if data such as sequences from samples of environmental DNA (eDNA) are available. Implementing the TH paradigm will to some extent remove the impediment to hastily discover and formally describe all extant species in that the TH paradigm allows discovery and communication of new species and other taxa also in the absence of formal descriptions. The TH datasets can be connected to a taxonomic backbone providing access to the vast information associated with the tree of life. In parallel to the description of the TH paradigm, we demonstrate how it is implemented in the UNITE digital taxon communication system. UNITE TH datasets include rich data on individuals and their rDNA ITS sequences. These datasets are equipped with digital object identifiers (DOI) that serve to fix their identity in our communication. All datasets are also connected to a GBIF taxonomic backbone. Researchers processing their eDNA samples using UNITE datasets will, thus, be able to publish their findings as taxon occurrences in the GBIF data portal. UNITE species hypothesis (species level THs) datasets are increasingly utilized in taxon identification pipelines and even formally undescribed species can be identified and communicated by using UNITE. The TH paradigm seeks to achieve unambiguous, unique, and traceable communication of taxa and their properties at any level of the tree of life. It offers a rapid way to discover and communicate undescribed species in identification pipelines and data portals before they are lost to the sixth mass extinction. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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29.
  • Kõljalg, Urmas, et al. (författare)
  • Towards a unified paradigm for sequence-based identification of fungi.
  • 2013
  • Ingår i: Molecular ecology. - : Wiley. - 1365-294X .- 0962-1083. ; 22:21, s. 5271-7
  • Tidskriftsartikel (refereegranskat)abstract
    • The nuclear ribosomal internal transcribed spacer (ITS) region is the formal fungal barcode and in most cases the marker of choice for the exploration of fungal diversity in environmental samples. Two problems are particularly acute in the pursuit of satisfactory taxonomic assignment of newly generated ITS sequences: (i) the lack of an inclusive, reliable public reference data set and (ii) the lack of means to refer to fungal species, for which no Latin name is available in a standardized stable way. Here, we report on progress in these regards through further development of the UNITE database (http://unite.ut.ee) for molecular identification of fungi. All fungal species represented by at least two ITS sequences in the international nucleotide sequence databases are now given a unique, stable name of the accession number type (e.g. Hymenoscyphus pseudoalbidus|GU586904|SH133781.05FU), and their taxonomic and ecological annotations were corrected as far as possible through a distributed, third-party annotation effort. We introduce the term 'species hypothesis' (SH) for the taxa discovered in clustering on different similarity thresholds (97-99%). An automatically or manually designated sequence is chosen to represent each such SH. These reference sequences are released (http://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and in the QIIME pipeline. The system and the data will be updated automatically as the number of public fungal ITS sequences grows. We invite everybody in the position to improve the annotation or metadata associated with their particular fungal lineages of expertise to do so through the new Web-based sequence management system in UNITE.
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30.
  • Kõljalg, Urmas, et al. (författare)
  • UNITE: a database providing web-based methods for the molecular identification of ectomycorrhizal fungi
  • 2005
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 166:3, s. 1063-1068
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of ectomycorrhizal (ECM) fungi is often achieved through comparisons of ribosomal DNA internal transcribed spacer (ITS) sequences with accessioned sequences deposited in public databases. A major problem encountered is that annotation of the sequences in these databases is not always complete or trustworthy. In order to overcome this deficiency, we report on UNITE, an open-access database. UNITE comprises well annotated fungal ITS sequences from well defined herbarium specimens that include full herbarium reference identification data, collector/source and ecological data. At present UNITE contains 758 ITS sequences from 455 species and 67 genera of ECM fungi. UNITE can be searched by taxon name, via sequence similarity using BLAST n, and via phylogenetic sequence identification using galaxie. Following implementation, galaxie performs a phylogenetic analysis of the query sequence after alignment either to pre-existing generic alignments, or to matches retrieved from a BLAST search on the UNITE data. It should be noted that the current version of UNITE is dedicated to the reliable identification of ECM fungi. The UNITE database is accessible through the URLhttp://unite.zbi.ee.
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31.
  • Moncalvo, J. M., et al. (författare)
  • The cantharelloid clade: dealing with incongruent gene trees and phylogenetic reconstruction methods
  • 2006
  • Ingår i: Mycologia. - : Informa UK Limited. - 0027-5514 .- 1557-2536. ; 98:6, s. 937-948
  • Tidskriftsartikel (refereegranskat)abstract
    • We reassessed the circumscription of the cantharelloid clade and identified monophyletic groups by using nLSU, nSSU, mtSSU and RPB2 sequence data. Results agreed with earlier studies that placed the genera Cantharellus, Craterellus, Hydnum, Clavulina, Membranomyces, Multiclavula, Sistotrema, Botryobasidium and the family Ceratobasidiaceae in that clade. Phylogenetic analyses support monophyly of all genera except Sistotrema, which was highly polyphyletic. Strongly supported monophyletic groups were: (i) Cantharellus-Craterellus, Hydnum, and the Sistotrema confluens group; (ii) Clavulina-Membranomyces and the S. brinkmannii-oblongisporum group, with Multiclavula being possibly sister of that clade; (iii) the Sistotrema eximum-octosporum group; (iv) Sistotrema adnatum and S. coronilla. Positions of Sistotrema raduloides and S. athelioides were unresolved, as were basal relationships. Botryobasidium was well supported as the sister taxon of all the above taxa, while Ceratobasidiaceae was the most basal lineage. The relationship between Tulasnella and members of the cantharelloid clade will require further scrutiny, although there is cumulative evidence that they are probably sister groups. The rates of molecular evolution of both the large and small nuclear ribosomal RNA genes (nuc-rDNA) are much higher in Cantharellus, Craterellus and Tulasnella than in the other cantharelloid taxa, and analyses of nuc-rDNA sequences strongly placed Tulasnella close to Cantharellus-Craterellus. In contrast analyses with RPB2 and mtSSU sequences placed Tulasnella at the base of the cantharelloid clade. Our attempt to reconstruct a "supertree" from tree topologies resulting from separate analyses that avoided phylogenetic reconstruction problems associated with missing data and/or unalignable sequences proved unsuccessful.
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32.
  • Münzenberger, Babette, et al. (författare)
  • Morphology, anatomy, and molecular studies of the ectomycorrhiza formed axenically by the fungus Sistotrema sp. (Basidiomycota)
  • 2012
  • Ingår i: Mycological Progress. - : Springer Science and Business Media LLC. - 1617-416X .- 1861-8952. ; 11:3, s. 817-826
  • Tidskriftsartikel (refereegranskat)abstract
    • Several species of the corticioid (resupinate) genus Sistotrema of the cantharelloid clade (Basidiomycota) were recently found to be ectomycorrhizal. This changed the traditional assertion that all Sistotrema species are strictly wood rotting and suggests that the genus may be polyphyletic. In the present investigation, a still unknown root tip-associated fungal specimen (EW63) was isolated and found to be associated with an above-ground fruiting body. Sequencing of the ITS and the nucLSU DNA regions and phylogenetic analyses verified that the root-associated fungus and the fruiting body represented the same species, which was found to belong to the genus Sistotrema. To prove the ectomycorrhizal status of this strain, axenic Pinus sylvestris resyntheses in flask cultures were conducted. Growth parameters of the seedlings were determined and the morphology and anatomy of the synthesized mycorrhizas were described. Length and dry mass of the Pinus shoot as well as those of the total root tips were found to be enhanced as a result of the mycorrhizal association. Mycorrhizal frequency was high (51.5%) in these cultures. Mycorrhizal root tips were cottony light ochre with a thin plectenchymatic hyphal mantle. The clamps of the fruiting body hyphae as well as the mycorrhiza were ampullately inflated. This is the first report proving in axenic culture that a fungus belonging to the genus Sistotrema forms true ectomycorrhiza.
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33.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • A software pipeline for processing and identification of fungal ITS sequences
  • 2009
  • Ingår i: Source Code for Biology and Medicine. - 1751-0473. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Fungi from environmental samples are typically identified to species level through DNA sequencing of the nuclear ribosomal internal transcribed spacer (ITS) region for use in BLAST-based similarity searches in the International Nucleotide Sequence Databases. These searches are time-consuming and regularly require a significant amount of manual intervention and complementary analyses. We here present software - in the form of an identification pipeline for large sets of fungal ITS sequences - developed to automate the BLAST process and several additional analysis steps. The performance of the pipeline was evaluated on a dataset of 350 ITS sequences from fungi growing as epiphytes on building material. Results The pipeline was written in Perl and uses a local installation of NCBI-BLAST for the similarity searches of the query sequences. The variable subregion ITS2 of the ITS region is extracted from the sequences and used for additional searches of higher sensitivity. Multiple alignments of each query sequence and its closest matches are computed, and query sequences sharing at least 50 % of their best matches are clustered to facilitate the evaluation of hypothetically conspecific groups. The pipeline proved to speed up the processing, as well as enhance the resolution, of the evaluation dataset considerably, and the fungi were found to belong chiefly to the Ascomycota, with Penicillium and Aspergillus as the two most common genera. The ITS2 was found to indicate a different taxonomic affiliation than did the complete ITS region for 10 % of the query sequences, though this figure is likely to vary with the taxonomic scope of the query sequences. Conclusions The present software readily assigns large sets of fungal query sequences to their respective best matches in the international sequence databases and places them in a larger biological context. The output is highly structured to be easy to process, although it still needs to be inspected and possibly corrected for the impact of the incomplete and sometimes erroneously annotated fungal entries in these databases. The open source pipeline is available for UNIX-type platforms, and updated releases of the target database are made available biweekly. The pipeline is easily modified to operate on other molecular regions and organism groups.
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34.
  •  
35.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Fruiting body-guided molecular identification of root-tip mantle mycelia provides strong indications of ectomycorrhizal associations in two species of Sistotrema (Basidiomycota)
  • 2006
  • Ingår i: Mycological Research. - : Elsevier BV. - 0953-7562. ; 110, s. 1426-1432
  • Tidskriftsartikel (refereegranskat)abstract
    • Fruiting body guided sequence analysis of mycorrhizal root-tip mycelia is a powerful yet relatively sparsely explored method for species-level identification of mycorrhizal fungi. It is used in this study to indicate mycorrhizal associations in the corticioid (resupinate) genus Sistotrema of the cantharelloid clade through phylogenetic analysis of the ITS and nuLSU rDNA regions of two spatiotemporally co-occurring Sistotrema fruiting bodies and ectomycorrhizal root tips. The genus Sistotrema is confirmed to be polyphyletic, and the mycorrhizal species form a strongly supported monophyletic clade together with the stipitate genus Hydnum. The remaining lineages of Sistotrema may well be saprotrophic, the nutritional mode traditionally attributed to the genus, but the phylogenetic analyses show that they should be excluded from Sistotrema. The cantharelloid clade contains several mycorrhizal genera, but no symbiotic associations have previously been demonstrated for Sistotrema. (c) 2006 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
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36.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • galaxie - CGI scripts for sequence identification through automated phylogenetic analysis
  • 2004
  • Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 20:9, s. 1447-1452
  • Tidskriftsartikel (refereegranskat)abstract
    • Motivation: The prevalent use of similarity searches like BLAST to identify sequences and species implicitly assumes the reference database to be of extensive sequence sampling. This is often not the case, restraining the correctness of the outcome as a basis for sequence identification. Phylogenetic inference outperforms similarity searches in retrieving correct phylogenies and consequently sequence identities, and a project was initiated to design a freely available script package for sequence identification through automated Web-based phylogenetic analysis. Results: Three CGI scripts were designed to facilitate qualified sequence identification from a Web interface. Query sequences are aligned to pre-made alignments or to alignments made by ClustalW with entries retrieved from a BLAST search. The subsequent phylogenetic analysis is based on the PHYLIP package for inferring neighbor-joining and parsimony trees. The scripts are highly configurable.
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37.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • galaxieEST: addressing EST identity through automated phylogenetic analysis
  • 2004
  • Ingår i: Bmc Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Research involving expressed sequence tags ( ESTs) is intricately coupled to the existence of large, well-annotated sequence repositories. Comparatively complete and satisfactory annotated public sequence libraries are, however, available only for a limited range of organisms, rendering the absence of sequences and gene structure information a tangible problem for those working with taxa lacking an EST or genome sequencing project. Paralogous genes belonging to the same gene family but distinguished by derived characteristics are particularly prone to misidentification and erroneous annotation; high but incomplete levels of sequence similarity are typically difficult to interpret and have formed the basis of many unsubstantiated assumptions of orthology. In these cases, a phylogenetic study of the query sequence together with the most similar sequences in the database may be of great value to the identification process. In order to facilitate this laborious procedure, a project to employ automated phylogenetic analysis in the identification of ESTs was initiated. Results: galaxieEST is an open source Perl-CGI script package designed to complement traditional similarity-based identification of EST sequences through employment of automated phylogenetic analysis. It uses a series of BLAST runs as a sieve to retrieve nucleotide and protein sequences for inclusion in neighbour joining and parsimony analyses; the output includes the BLAST output, the results of the phylogenetic analyses, and the corresponding multiple alignments. galaxieEST is available as an on-line web service for identification of fungal ESTs and for download/local installation for use with any organism group at http://galaxie.cgb.ki.se/galaxieEST.html. Conclusions: By addressing sequence relatedness in addition to similarity, galaxieEST provides an integrative view on EST origin and identity, which may prove particularly useful in cases where similarity searches return one or more pertinent, but not full, matches and additional information on the query EST is needed.
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38.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • How, not if, is the question mycologists should be asking about DNA-based typification
  • 2023
  • Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; :96, s. 143-157
  • Tidskriftsartikel (refereegranskat)abstract
    • Fungal metabarcoding of substrates such as soil, wood, and water is uncovering an unprecedented number of fungal species that do not seem to produce tangible morphological structures and that defy our best attempts at cultivation, thus falling outside the scope of the International Code of Nomenclature for algae, fungi, and plants. The present study uses the new, ninth release of the species hypotheses of the UNITE database to show that species discovery through environmental sequencing vastly outpaces traditional, Sanger sequencing-based efforts in a strongly increasing trend over the last five years. Our findings chal-lenge the present stance of some in the mycological community - that the current situation is satisfactory and that no change is needed to "the code" - and suggest that we should be discussing not whether to allow DNA-based descriptions (typifications) of species and by extension higher ranks of fungi, but what the precise requirements for such DNA-based typifications should be. We submit a tentative list of such criteria for further discussion. The present authors hope for a revitalized and deepened discussion on DNA-based typification, because to us it seems harmful and counter-productive to intentionally deny the overwhelming majority of extant fungi a formal standing under the International Code of Nomenclature for algae, fungi, and plants.
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39.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Improving ITS sequence data for identification of plant pathogenic fungi
  • 2014
  • Ingår i: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 67:1, s. 11-19
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant pathogenic fungi are a large and diverse assemblage of eukaryotes with substantial impacts on natural ecosystems and human endeavours. These taxa often have complex and poorly understood life cycles, lack observable, discriminatory morphological characters, and may not be amenable to in vitro culturing. As a result, species identification is frequently difficult. Molecular (DNA sequence) data have emerged as crucial information for the taxonomic identification of plant pathogenic fungi, with the nuclear ribosomal internal transcribed spacer (ITS) region being the most popular marker. However, international nucleotide sequence databases are accumulating numerous sequences of compromised or low-resolution taxonomic annotations and substandard technical quality, making their use in the molecular identification of plant pathogenic fungi problematic. Here we report on a concerted effort to identify high-quality reference sequences for various plant pathogenic fungi and to re-annotate incorrectly or insufficiently annotated public ITS sequences from these fungal lineages. A third objective was to enrich the sequences with geographical and ecological metadata. The results – a total of 31,954 changes – are incorporated in and made available through the UNITE database for molecular identification of fungi (http://unite.ut.ee), including standalone FASTA files of sequence data for local BLAST searches, use in the next-generation sequencing analysis platforms QIIME and mothur, and related applications. The present initiative is just a beginning to cover the wide spectrum of plant pathogenic fungi, and we invite all researchers with pertinent expertise to join the annotation effort.
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40.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Molecular identification of fungi: rationale, philosophical concerns, and the UNITE database
  • 2011
  • Ingår i: The Open Applied Informatics Journal. - : Bentham Science Publishers Ltd.. - 1874-1363. ; 5, s. 81-86
  • Forskningsöversikt (refereegranskat)abstract
    • Fungi form a ubiquitous group of largely inconspicuous organisms that play key ecological roles in terrestrial nutrient cycling. The typically subterranean or otherwise unnoticeable nature of fungal life has left mycology with a partial understanding of fungal biology, and progress is hampered by factors such as the difficulty to delimit species and individuals of fungi and the sparsity of discriminatory morphological and physiological characters for reliable species identification. These and other complications have paved the way for DNA sequence data as an important source of information in mycology, and there are now twenty years’ worth of fungal sequence data available for scientific purposes. However, issues of data reliability and generality impede the use of publicly available fungal DNA sequences. The UNITE database for molecular identification of fungi (http://unite.ut.ee) was built as a response to the difficulties facing anyone seeking to identify environmental samples of fungi to species level using molecular data and the major international sequence databases. The present study describes the UNITE database and examines the role of UNITE in the light of emerging sequencing technologies, notably massively parallel (“454”) pyrosequencing. Environmental sampling of fungi is discussed from a taxonomic perspective.
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41.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Read quality-based trimming of the distal ends of public fungal DNA sequences is nowhere near satisfactory
  • 2017
  • Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 26, s. 13-24
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA sequences are increasingly used for taxonomic and functional assessment of environmental communities. In mycology, the nuclear ribosomal internal transcribed spacer (ITS) region is the most commonly chosen marker for such pursuits. Molecular identification is associated with many challenges, one of which is low read quality of the reference sequences used for inference of taxonomic and functional properties of the newly sequenced community (or single taxon). This study investigates whether public fungal ITS sequences are subjected to sufficient trimming in their distal (5’ and 3’) ends prior to deposition in the public repositories. We examined 86 species (and 10,584 sequences) across the fungal tree of life, and we found that on average 13.1% of the sequences were poorly trimmed in one or both of their 5’ and 3’ ends. Deposition of poorly trimmed entries was found to continue through 2016. Poorly trimmed reference sequences add noise and mask biological signal in sequence similarity searches and phylogenetic analyses, and we provide a set of recommendations on how to manage the sequence trimming problem.
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42.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Rethinking taxon sampling in the light of environmental sequencing
  • 2011
  • Ingår i: Cladistics. - : Wiley. - 1096-0031 .- 0748-3007. ; 27:2, s. 197-203
  • Tidskriftsartikel (refereegranskat)abstract
    • Environmental DNA sequencing efforts of substrates such as soil, wood, and seawater have been found to present very different views of the underlying biological communities compared with efforts based on morphological examination and culture studies. The taxonomic affiliation of many of these environmental sequences cannot be settled with certainty due to the lack of proximate reference sequences in the corpus of public sequence data, and they are typically submitted to the international sequence databases without much indication of their relatedness. The scientific community has proved reluctant to include such unnamed sequences in phylogenetic analyses and taxonomic studies, but the present study shows such a position to be not only largely unwarranted but also potentially unsound. The sequences of 48 published fungal alignments of the nuclear ribosomal internal transcribed spacer region were subjected to similarity searches in the sequence databases to recover environmental sequences with a clear bearing on the respective ingroup. An average of 20 environmental sequences were added to each alignment, and upon rerunning the phylogenetic analyses of each study we found that topological rearrangements involving the original ingroup sequences were observed for no less than 29 (60%) of the studies. In nearly 20% of these cases, the rearrangements were large enough to question or even overthrow at least one conclusion presented in the original studies. The basal branching order was similarly subject to changes in 16% of the applicable studies. Environmental sequences are thus not only relevant in ecological research but form a requisite source of information also in systematics and taxonomy.
  •  
43.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • The ITS region as a target for characterization of fungal communities using emerging sequencing technologies
  • 2009
  • Ingår i: FEMS Microbiology Letters. - 0378-1097 .- 1574-6968. ; 296:1, s. 97-101
  • Tidskriftsartikel (refereegranskat)abstract
    • The advent of new high-throughput DNA-sequencing technologies promises to redefine the way in which fungi and fungal communities – as well as other groups of organisms – are studied in their natural environment. With read lengths of some few hundred base pairs, massively parallel sequencing (pyrosequencing) stands out among the new technologies as the most apt for large-scale species identification in environmental samples. Although parallel pyrosequencing can generate hundreds of thousands of sequences at an exceptional speed, the limited length of the reads may pose a problem to the species identification process. This study explores whether the discrepancy in read length between parallel pyrosequencing and traditional (Sanger) sequencing will have an impact on the perceived taxonomic affiliation of the underlying species. Based on all 39 200 publicly available fungal environmental DNA sequences representing the nuclear ribosomal internal transcribed spacer (ITS) region, the results show that the two approaches give rise to quite different views of the diversity of the underlying samples. Standardization of which subregion from the ITS region should be sequenced, as well as a recognition that the composition of fungal communities as depicted through different sequencing methods need not be directly comparable, appear crucial to the integration of the new sequencing technologies with current mycological praxis.
  •  
44.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • The UNITE database for molecular identification of fungi: handling dark taxa and parallel taxonomic classifications.
  • 2019
  • Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 47:D1
  • Tidskriftsartikel (refereegranskat)abstract
    • UNITE (https://unite.ut.ee/) is a web-based database and sequence management environment for the molecular identification of fungi. It targets the formal fungal barcode-the nuclear ribosomal internal transcribed spacer(ITS) region-and offers all ∼1 000000 public fungal ITS sequences for reference. These are clustered into ∼459000 species hypotheses and assigned digital object identifiers (DOIs) to promote unambiguous reference across studies. In-house and web-based third-party sequence curation and annotation have resulted in more than 275000 improvements to the data over the past 15 years. UNITE serves as a data provider for a range of metabarcoding software pipelines and regularly exchanges data with all major fungal sequence databases and other community resources. Recent improvements include redesigned handling of unclassifiable species hypotheses, integration with the taxonomic backbone of the Global Biodiversity Information Facility, and support for an unlimited number of parallel taxonomic classification systems.
  •  
45.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Top 50 most wanted fungi
  • 2016
  • Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 12, s. 29-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Environmental sequencing regularly recovers fungi that cannot be classified to any meaningful taxonomic level beyond “Fungi”. There are several examples where evidence of such lineages has been sitting in public sequence databases for up to ten years before receiving scientific attention and formal recognition. In order to highlight these unidentified lineages for taxonomic scrutiny, a search function is presented that produces updated lists of approximately genus-level clusters of fungal ITS sequences that remain unidentified at the phylum, class, and order levels, respectively. The search function (https://unite.ut.ee/top50.php) is implemented in the UNITE database for molecular identification of fungi, such that the underlying sequences and fungal lineages are open to third-party annotation. We invite researchers to examine these enigmatic fungal lineages in the hope that their taxonomic resolution will not have to wait another ten years or more.
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46.
  •  
47.
  • Nilsson, Thomas, 1954, et al. (författare)
  • Neurochemical measures co-vary with personality traits: Forensic psychiatric findings replicated in a general population sample
  • 2010
  • Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 178:3, s. 525-530
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurobiological markers in cerebrospinal fluid (CSF) and in serum, previously found to co-vary with destructive personality traits in violent offenders, were explored in a general population sample of 21 patients undergoing knee surgery. Results on the Karolinska Scales of Personality (KSP) and the Temperament and Character Inventory (TCI) were compared with CSF/serum albumin ratios and serum concentrations of beta-trace protein (beta TP) (as markers for blood-brain barrier (BBB) permeability), to CSF/serum albumin ratios between the dopamine and serotonin metabolites homovanillic acid (HVA)/5-hydroxyindoleacetic acid (HIM) and to CSF and serum ratios between activated thyroid hormone (T3) and its precursor T4. Serum beta TP concentrations correlated with CSF/serum albumin ratios (P=0.018), but not with preoperative serum creatinine concentrations. Serum beta TP correlated significantly with Monotony Avoidance and Impulsiveness: CSF HVA/5-HIAA ratios with Irritability and low Cooperativeness. The beta TP is a potential serum marker for the integrity of the BBB that does not necessitate lumbar puncture. Thyroid hormones did not correlate with personality traits. As reported in forensic psychiatric patients, aggressive, unempathic personality traits were thus associated with increased dopaminergic activity in relation to the serotonergic activity and impulsivity to increased BBB permeability also in a general population group. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
  •  
48.
  • Ny, Lars, 1967, et al. (författare)
  • Supporting clinical decision making in advanced melanoma by preclinical testing in personalized immune-humanized xenograft mouse models
  • 2020
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:2, s. 266-273
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The mouse strains usually used to generate patient-derived xenografts (PDXs) are immunocompromised, rendering them unsuitable for immunotherapy studies. Here we assessed the value of immune-PDX mouse models for predicting responses to anti-PD-1 checkpoint inhibitor therapy in patients. Patients and methods: Melanoma biopsies contained in a retrospective biobank were transplanted into NOG mice or NOG mice expressing interleukin 2 (hIL2-NOG mice). Tumor growth was monitored, and comparisons were made with clinical data, sequencing data, and current in silico predictive tools. Results: Biopsies grew readily in NOG mice but growth was heterogeneous in hIL2-NOG mice. IL2 appears to activate T-cell immunity in the biopsies to block tumor growth. Biopsy growth in hIL2-NOG mice was negatively associated with survival in patients previously treated with PD-1 checkpoint blockade. In two cases, the prospective clinical decisions of anti-PD-1 therapy or targeted BRAF/MEK inhibitors were supported by the observed responses in mice. Conclusions: Immune-PDX models represent a promising addition to future biomarker discovery studies and for clinical decision making in patients receiving immunotherapy.
  •  
49.
  • Ny, Lars, 1967, et al. (författare)
  • The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The authors report the results of the phase II PEMDAC clinical study testing the combination of the HDAC inhibitor entinostat with the anti- PD-1 antibody pembrolizumab in uveal melanoma. Low tumor burden, a wildtype BAP1 gene in the tumor or iris melanoma correlates with response and longer survival. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.
  •  
50.
  • Parmasto, Erast, et al. (författare)
  • Cortbase version 2 – extensive updates of a nomenclatural database for corticioid fungi (Hymenomycetes)
  • 2004
  • Ingår i: PhyloInformatics. ; 5, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Cortbase is a nomenclatural database for corticioid (resupinate) fungi (Corticiaceae s.l. and related hymenomycetes) with basionyms, synonyms, taxonomically correct names, data on name usage, literature references, and evaluation of nomenclatural status. It is available as an on-line service (http://andromeda.botany.gu.se/cortbase.html) and as an MS-DOS executable for local installation. The database includes 8112 species names; of the 4412 basionyms included, 2101 represent taxonomically acceptable species, 1434 are heterotypic synonyms, and 877 are of uncertain application. The improvements over the previous version include the new, platformindependent on-line search interface, some 800 more corticioid names, numerous additions to the existing data, and six new categories for searching, including searches for location of type specimens and for authors of species names.
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