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Sökning: WFRF:(Rahbek Carsten)

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  • Eskelund, Christian Winther, et al. (författare)
  • Detailed Long-Term Follow-Up of Patients Who Relapsed After the Nordic Mantle Cell Lymphoma Trials : MCL2 and MCL3
  • 2021
  • Ingår i: HEMASPHERE. - : Ovid Technologies (Wolters Kluwer Health). - 2572-9241. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Mantle cell lymphoma (MCL) is an incurable disease with a highly variable clinical course. The prognosis after relapse is generally poor, and no standard of care exists. We investigated the postrelapse outcomes of 149 patients who were initially treated in the Nordic Lymphoma Group trials, MCL2 or MCL3, both representing intensive cytarabine-containing frontline regimens including autologous stem cell transplant. Patients with progression of disease before 24 months (POD24, n = 51, 34%) displayed a median overall survival of 6.6 months compared with 46 months for patients with later POD (n = 98, 66%; P < 0.001). MCL international prognostic index, cell proliferation marker, blastoid morphology, and TP53 mutations showed independent prognostic value irrespective of POD24, and in a combined, exploratory risk score, patients with 0, 1, 2-3, or 4-5 high-risk markers, respectively, displayed a 5-year overall survival of 62%, 39%, 31%, and 0%. By a comparison of median progression-free survival of the different salvage therapies in the relapse setting, bendamustine-rituximab was superior to all other combination chemotherapy regimens; however, it was also associated with longer responses to last line of therapy. Collectively, we confirm the prognostic impact of POD24 and highlight the relevance of other biomarkers, and we emphasize the importance of novel therapies for patients with high-risk features at first POD.
  • Feng, Shaohong, et al. (författare)
  • Dense sampling of bird diversity increases power of comparative genomics
  • 2020
  • Ingår i: Nature. - : NATURE RESEARCH. - 0028-0836 .- 1476-4687. ; 587:7833, s. 252-257
  • Tidskriftsartikel (refereegranskat)abstract
    • Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
  • Gluud, Maria, et al. (författare)
  • MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas
  • 2020
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 12:5
  • Forskningsöversikt (refereegranskat)abstract
    • Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL.
  • Jarvis, Erich D., et al. (författare)
  • Whole-genome analyses resolve early branches in the tree of life of modern birds
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
  • Tidskriftsartikel (refereegranskat)abstract
    • To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
  • Jønsson, Knud A, et al. (författare)
  • Ecological and evolutionary determinants for the adaptive radiation of the Madagascan vangas.
  • 2012
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 109:17, s. 6620-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Adaptive radiation is the rapid diversification of a single lineage into many species that inhabit a variety of environments or use a variety of resources and differ in traits required to exploit these. Why some lineages undergo adaptive radiation is not well-understood, but filling unoccupied ecological space appears to be a common feature. We construct a complete, dated, species-level phylogeny of the endemic Vangidae of Madagascar. This passerine bird radiation represents a classic, but poorly known, avian adaptive radiation. Our results reveal an initial rapid increase in evolutionary lineages and diversification in morphospace after colonizing Madagascar in the late Oligocene some 25 Mya. A subsequent key innovation involving unique bill morphology was associated with a second increase in diversification rates about 10 Mya. The volume of morphospace occupied by contemporary Madagascan vangas is in many aspects as large (shape variation)--or even larger (size variation)--as that of other better-known avian adaptive radiations, including the much younger Galapagos Darwin's finches and Hawaiian honeycreepers. Morphological space bears a close relationship to diet, substrate use, and foraging movements, and thus our results demonstrate the great extent of the evolutionary diversification of the Madagascan vangas.
  • Le Pepke, Michael, et al. (författare)
  • Reconciling supertramps, great speciators and relict species with the taxon cycle stages of a large island radiation (Aves: Campephagidae)
  • 2019
  • Ingår i: Journal of Biogeography. - : WILEY. - 0305-0270 .- 1365-2699. ; 46:6, s. 1214-1225
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim The taxon cycle concept provides a geographically explicit and testable set of hypotheses for exploring the evolutionary processes underlying the distribution of species in space and time. Here, we test taxon cycle predictions within a large avian island radiation, the core Campephagidae and explicitly integrate the concepts of ‘supertramps’, ‘great speciators’ and relictualization. Location The Indo-Pacific, Australia, Asia and Africa. Taxon Corvoid passerine birds. Methods We constructed a new time-calibrated molecular phylogeny of the core Campephagidae (cuckooshrikes, cicadabirds and trillers) using Bayesian phylogenetic methods. Ancestral range estimation methods and diversification rate analyses were used to explore the dispersal and diversification history of the group. We used an extensive dataset on wing morphology and range distributions to test for correlations between evolutionary age of species and dispersal capacity, diversification and distribution, while accounting for phylogenetic non-independence. Results The core Campephagidae represents an ecologically homogeneous radiation distributed across the Indo-Pacific, Australia, Southeast Asia and Africa. Its members represent a continuum of dispersal abilities; some species are widespread and undifferentiated (’supertramps’) or show strong differentiation of local populations (’great speciators’), and a few are endemic to single islands (relicts). We show that older species relative to younger species inhabit fewer and larger islands at higher elevations. The level of intraspecific variation measured as the number of subspecies also decreases with species age, and is highest in ‘great speciators’ with intermediate levels of dispersal abilities (as per hand-wing index). Main conclusions Based on trait correlations with species age, we infer phases of range expansion and contraction over millions of years (taxon cycles), within a single monophyletic group of birds. These observations demonstrate reconciliation of the concepts of ‘supertramps’, ‘great speciators’ and relictual palaeoendemics within the temporal stages of the taxon cycle.
  • Lorenzen, Eline D., et al. (författare)
  • Species-specific responses of Late Quaternary megafauna to climate and humans
  • 2011
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 479:7373, s. 359-364
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.
  • Marki, Petter Z., et al. (författare)
  • Supermatrix phylogeny and biogeography of the Australasian Meliphagides radiation (Aves: Passeriformes)
  • 2017
  • Ingår i: Molecular Phylogenetics and Evolution. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1055-7903 .- 1095-9513. ; 107, s. 516-529
  • Tidskriftsartikel (refereegranskat)abstract
    • With nearly 300 species, the infraorder Meliphagides represents one of the largest and most conspicuous Australasian bird radiations. Although the group has been the focus of a number of recent phylogenetic studies, a comprehensive species-level phylogenetic hypothesis is still lacking. This has impeded the assessment of broad-scale evolutionary, biogeographic and ecological hypotheses. In the present study, we use a supermatrix approach including five mitochondrial and four nuclear markers to infer a time calibrated phylogeny of the Meliphagides. Our phylogeny, which includes 286 of the 289 (99%) currently recognized species, is largely congruent with previous estimates. However, the addition of 60 newly sequenced species reveals some novel relationships. Our biogeographic analyses suggest an Australian origin for the group in the early Oligocene (31.3 Mya, 95% HPD 25.2-38.2 Mya). In addition, we find that dispersal events out of Australia have been numerous and frequent, particularly to New Guinea, which has also been the source of multiple back-colonizations to the Australian mainland. The phylogeny provides an important framework for studying a wide variety of macroecological and macroevolutionary themes, including character evolution, origin and timing of diversification, biogeographic patterns and species responses to climate change. (C) 2016 Elsevier Inc. All rights reserved.
  • Pedersen, Michael Pepke, et al. (författare)
  • Phylogeography of a "€˜great speciator"€™ (Aves: Edolisoma tenuirostre) reveals complex dispersal and diversification dynamics across the Indo-Pacific
  • 2018
  • Ingår i: Journal of Biogeography. - : Wiley-Blackwell. ; 45:4, s. 826-837
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Aim We derive a new phylogenetic framework of the Indo-Pacific avian genus Edolisoma based on a dense taxon sampling and use it in an explicit spatiotemporal framework to understand the history of intraspecific diversification dynamics in a ‘great speciator’, the Cicadabird Edolisoma tenuirostre/remotum complex. Location The Indo-Pacific island region, Australia and New Guinea. Taxon Corvoid passerine birds (Passeriformes). Methods We used Bayesian phylogenetic methods (beast) to construct a time-calibrated molecular phylogeny of all 19 species in the genus Edolisoma and 27 of 29 subspecies of the E. tenuirostre/remotum complex (previously Coracina tenuirostris) primarily based on one mitochondrial DNA marker. Ancestral area reconstruction methods (‘BioGeoBEARS’) were used to infer the historical biogeography of the genus. We used population-level analyses to assess intraspecific phylogeography and a molecular species delimitation test to evaluate the current taxonomy. A morphometric dataset was used to discuss differential dispersal ability among taxa. Results Edolisoma originated in the late Miocene and diversification within the E. tenuirostre/remotum complex began in the Pleistocene. Within the North Melanesian and North Wallacean archipelagos, which have experienced several waves of diversification, we find significant patterns of genetic isolation by distance, but not within the Australo-Papuan ‘mainland’, which was recently back-colonized from these archipelagos. Based on the phylogeny, we suggest several taxonomic changes. We also discuss evidence of taxon cycles within Edolisoma based on correlations of species age, elevational ranges and dispersal ability. Main conclusions The biogeographical history and patterns of differentiation between phylogroups within E. tenuirostre support the importance of barriers to gene flow in island systems. Examples of both recent genetic exchange across significant sea barriers and differentiation across much smaller water gaps suggest complex dispersal and diversification dynamics. The capacity for dispersal away from islands, and gradual shifts in dispersal ability in relation to the geographical setting, is supported as important factors in generating a ‘great speciator’.
  • Pettersson, Lars, et al. (författare)
  • Launching Software Notes
  • 2008
  • Ingår i: Ecography. - : Wiley-Blackwell. - 1600-0587. ; 31:1, s. 3-3
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract is not available
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