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1.
  • Canfield, Donald E., et al. (författare)
  • A Mesoproterozoic iron formation
  • 2018
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 115:17, s. 3895-3904
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe a 1,400 million-year old (Ma) iron formation (IF) from the Xiamaling Formation of the North China Craton. We estimate this IF to have contained at least 520 gigatons of authigenic Fe, comparable in size to many IFs of the Paleoproterozoic Era (2,500–1,600 Ma). Therefore, substantial IFs formed in the time window between 1,800 and 800 Ma, where they are generally believed to have been absent. The Xiamaling IF is of exceptionally low thermal maturity, allowing the preservation of organic biomarkers and an unprecedented view of iron-cycle dynamics during IF emplacement. We identify tetramethyl aryl isoprenoid (TMAI) biomarkers linked to anoxygenic photosynthetic bacteria and thus phototrophic Fe oxidation. Although we cannot rule out other pathways of Fe oxidation, iron and organic matter likely deposited to the sediment in a ratio similar to that expected for anoxygenic photosynthesis. Fe reduction was likely a dominant and efficient pathway of organic matter mineralization, as indicated by organic matter maturation by Rock Eval pyrolysis combined with carbon isotope analyses: Indeed, Fe reduction was seemingly as efficient as oxic respiration. Overall, this Mesoproterozoic-aged IF shows many similarities to Archean-aged (>2,500 Ma) banded IFs (BIFs), but with an exceptional state of preservation, allowing an unprecedented exploration of Fe-cycle dynamics in IF deposition.
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2.
  • Carroll, Christopher, et al. (författare)
  • Hypoxia Generated by Avian Embryo Growth Induces the HIF-α Response and Critical Vascularization
  • 2021
  • Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 9, s. 1-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer research has transformed our view on cellular mechanisms for oxygen sensing. It has been documented that these mechanisms are important for maintaining animal tissues and life in environments where oxygen (O2) concentrations fluctuate. In adult animals, oxygen sensing is governed by the Hypoxia Inducible Factors (HIFs) that are stabilized at low oxygen concentrations (hypoxia). However, the importance of hypoxia itself during development and for the onset of HIF-driven oxygen sensing remains poorly explored. Cellular responses to hypoxia associates with cell immaturity (stemness) and proper tissue and organ development. During mammalian development, the initial uterine environment is hypoxic. The oxygenation status during avian embryogenesis is more complex since O2 continuously equilibrates across the porous eggshell. Here, we investigate HIF dynamics and use microelectrodes to determine O2 concentrations within the egg and the embryo during the first four days of development. To determine the increased O2 consumption rates, we also obtain the O2 transport coefficient (DO2) of eggshell and associated inner and outer shell membranes, both directly (using microelectrodes in ovo for the first time) and indirectly (using water evaporation at 37.5°C for the first time). Our results demonstrate a distinct hypoxic phase (<5% O2) between day 1 and 2, concurring with the onset of HIF-α expression. This phase of hypoxia is demonstrably necessary for proper vascularization and survival. Our indirectly determined DO2 values are about 30% higher than those determined directly. A comparison with previously reported values indicates that this discrepancy may be real, reflecting that water vapor and O2 may be transported through the eggshell at different rates. Based on our obtained DO2 values, we demonstrate that increased O2 consumption of the growing embryo appears to generate the phase of hypoxia, which is also facilitated by the initially small gas cell and low membrane permeability. We infer that the phase of in ovo hypoxia facilitates correct avian development. These results support the view that hypoxic conditions, in which the animal clade evolved, remain functionally important during animal development. The study highlights that insights from the cancer field pertaining to the cellular capacities by which both somatic and cancer cells register and respond to fluctuations in O2 concentrations can broadly inform our exploration of animal development and success.
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3.
  • Haxen, Emma R., et al. (författare)
  • “Hypoxic” Silurian oceans suggest early animals thrived in a low-O2 world
  • 2023
  • Ingår i: Earth and Planetary Science Letters. - 0012-821X. ; 622
  • Tidskriftsartikel (refereegranskat)abstract
    • Atmospheric oxygen (O2) concentrations likely remained below modern levels until the Silurian–Devonian, as indicated by several recent studies. Yet, the background redox state of early Paleozoic oceans remains poorly constrained, hampering our understanding of the relationship between early animal evolution and O2. Here, we present a multi-proxy analysis of redox conditions in the Caledonian foreland basin to Baltica from the early to the mid-Silurian. Our results indicate that anoxic to severely hypoxic bottom waters dominated during deposition of the Silurian sediments cored in the Sommerodde-1 well (Bornholm, Denmark), and regional comparison suggests that these conditions persisted across the Baltoscandian foreland basin. Indeed, even during times of relative oxygenation, ichnological observations indicate that conditions were, at most, very weakly oxic. The results suggest that dissolved O2 was generally scarce in the bottom waters of the extensive Silurian seaway between Baltica and Avalonia, even between Paleozoic “Anoxic Events”. In light of delayed oxygenation of the atmosphere–hydrosphere system, it may be time to consider that early animals were adapted to “hypoxia” and thrived through ∼100 million years of low-O2 conditions after the Cambrian.
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4.
  • Nasimian, Ahmad, et al. (författare)
  • AlphaML : A clear, legible, explainable, transparent, and elucidative binary classification platform for tabular data
  • 2024
  • Ingår i: Patterns. - 2666-3899. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Leveraging the potential of machine learning and recognizing the broad applications of binary classification, it becomes essential to develop platforms that are not only powerful but also transparent, interpretable, and user friendly. We introduce alphaML, a user-friendly platform that provides clear, legible, explainable, transparent, and elucidative (CLETE) binary classification models with comprehensive customization options. AlphaML offers feature selection, hyperparameter search, sampling, and normalization methods, along with 15 machine learning algorithms with global and local interpretation. We have integrated a custom metric for hyperparameter search that considers both training and validation scores, safeguarding against under- or overfitting. Additionally, we employ the NegLog2RMSL scoring method, which uses both training and test scores for a thorough model evaluation. The platform has been tested using datasets from multiple domains and offers a graphical interface, removing the need for programming expertise. Consequently, alphaML exhibits versatility, demonstrating promising applicability across a broad spectrum of tabular data configurations.
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5.
  • Niklasson, Camilla U., et al. (författare)
  • Hypoxia inducible factor-2 alpha importance for migration, proliferation, and self-renewal of trunk neural crest cells
  • 2021
  • Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 250:2, s. 191-236
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The neural crest is a transient embryonic stem cell population. Hypoxia inducible factor (HIF)-2 α is associated with neural crest stem cell appearance and aggressiveness in tumors. However, little is known about its role in normal neural crest development.Results: Here, we show that HIF-2 α is expressed in trunk neural crest cells of human, murine, and avian embryos. Knockdown as well as overexpression of HIF-2 α in vivo causes developmental delays, induces proliferation, and self-renewal capacity of neural crest cells while decreasing the proportion of neural crest cells that migrate ventrally to sympathoadrenal sites. Reflecting the in vivo phenotype, transcriptome changes after loss of HIF-2 α reveal enrichment of genes associated with cancer, invasion, epithelial-to-mesenchymal transition, and growth arrest.Conclusions: Taken together, these results suggest that expression levels of HIF-2 α must be strictly controlled during normal trunk neural crest development and that dysregulated levels affects several important features connected to stemness, migration, and development.
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6.
  • Philipsen, Mai H., et al. (författare)
  • Mapping the chemistry of hair strands by mass spectrometry imaging - A Review
  • 2021
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1420-3049. ; 26:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Hair can record chemical information reflecting our living conditions, and, therefore, strands of hair have become a potent analytical target within the biological and forensic sciences. While early efforts focused on analyzing complete hair strands in bulk, high spatial resolution mass spectrometry imaging (MSI) has recently come to the forefront of chemical hair-strand analysis. MSI techniques offer a localized analysis, requiring fewer de-contamination procedures per default and making it possible to map the distribution of analytes on and within individual hair strands. Applying the techniques to hair samples has proven particularly useful in investigations quantifying the exposure to, and uptake of, toxins or drugs. Overall, MSI, combined with optimized sample preparation protocols, has improved precision and accuracy for identifying several elemental and molecular species in single strands of hair. Here, we review different sample preparation protocols and use cases with a view to make the methodology more accessible to researchers outside of the field of forensic science. We conclude that-although some challenges remain, including contamination issues and matrix effects-MSI offers unique opportunities for obtaining highly resolved spatial information of several compounds simultaneously across hair surfaces.
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7.
  • Zhang, Shuichang, et al. (författare)
  • Paleoenvironmental proxies and what the Xiamaling Formation tells us about the mid-Proterozoic ocean
  • 2019
  • Ingår i: Geobiology. - : Wiley. - 1472-4677 .- 1472-4669. ; 17:3, s. 225-246
  • Tidskriftsartikel (refereegranskat)abstract
    • The Mesoproterozoic Era (1,600–1,000 million years ago, Ma) geochemical record is sparse, but, nevertheless, critical in untangling relationships between the evolution of eukaryotic ecosystems and the evolution of Earth-surface chemistry. The ca. 1,400 Ma Xiamaling Formation has experienced only very low-grade thermal maturity and has emerged as a promising geochemical archive informing on the interplay between climate, ecosystem organization, and the chemistry of the atmosphere and oceans. Indeed, the geochemical record of portions of the Xiamaling Formation has been used to place minimum constraints on concentrations of atmospheric oxygen as well as possible influences of climate and climate change on water chemistry and sedimentation dynamics. A recent study has argued, however, that some portions of the Xiamaling Formation deposited in a highly restricted environment with only limited value as a geochemical archive. In this contribution, we fully explore these arguments as well as the underlying assumptions surrounding the use of many proxies used for paleo-environmental reconstructions. In doing so, we pay particular attention to deep-water oxygen-minimum zone environments and show that these generate unique geochemical signals that have been underappreciated. These signals, however, are compatible with the geochemical record of those parts of the Xiamaling Formation interpreted as most restricted. Overall, we conclude that the Xiamaling Formation was most likely open to the global ocean throughout its depositional history. More broadly, we show that proper paleo-environmental reconstructions require an understanding of the biogeochemical signals generated in all relevant modern analogue depositional environments. We also evaluate new data on the δ 98 Mo of Xiamaling Formation shales, revealing possible unknown pathways of molybdenum sequestration into sediments and concluding, finally, that seawater at that time likely had a δ 98 Mo value of about 1.1‰.
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8.
  • Alcott, Lewis J., et al. (författare)
  • Development of Iron Speciation Reference Materials for Palaeoredox Analysis
  • 2020
  • Ingår i: Geostandards and Geoanalytical Research. - : Wiley. - 1639-4488 .- 1751-908X. ; 44:3, s. 581-591
  • Tidskriftsartikel (refereegranskat)abstract
    • The development and application of geochemical techniques to identify redox conditions in modern and ancient aquatic environments has intensified over recent years. Iron (Fe) speciation has emerged as one of the most widely used procedures to distinguish different redox regimes in both the water column and sediments, and is the main technique used to identify oxic, ferruginous (anoxic, Fe(II) containing) and euxinic (anoxic, sulfidic) water column conditions. However, an international sediment reference material has never been developed. This has led to concern over the consistency of results published by the many laboratories that now utilise the technique. Here, we report an interlaboratory comparison of four Fe speciation reference materials for palaeoredox analysis, which span a range of compositions and reflect deposition under different redox conditions. We provide an update of extraction techniques used in Fe speciation and assess the effects of both test portion mass, and the use of different analytical procedures, on the quantification of different Fe fractions in sedimentary rocks. While atomic absorption spectroscopy and inductively coupled plasma-optical emission spectrometry produced comparable Fe measurements for all extraction stages, the use of ferrozine consistently underestimated Fe in the extraction step targeting mixed ferrous–ferric minerals such as magnetite. We therefore suggest that the use of ferrozine is discontinued for this Fe pool. Finally, we report the combined data of four independent Fe speciation laboratories to characterise the Fe speciation composition of the reference materials. These reference materials are available to the community to provide an essential validation of in-house Fe speciation measurements.
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9.
  • Brown, Joel S., et al. (författare)
  • Updating the Definition of Cancer
  • 2023
  • Ingår i: Molecular cancer research : MCR. - 1557-3125. ; 21:11, s. 1142-1147
  • Tidskriftsartikel (refereegranskat)abstract
    • Most definitions of cancer broadly conform to the current NCI definition: "Cancer is a disease in which some of the body's cells grow uncontrollably and spread to other parts of the body." These definitions tend to describe what cancer "looks like" or "does" but do not describe what cancer "is" or "has become." While reflecting past insights, current definitions have not kept pace with the understanding that the cancer cell is itself transformed and evolving. We propose a revised definition of cancer: Cancer is a disease of uncontrolled proliferation by transformed cells subject to evolution by natural selection. We believe this definition captures the essence of the majority of previous and current definitions. To the simplest definition of cancer as a disease of uncontrolled proliferation of cells, our definition adds in the adjective "transformed" to capture the many tumorigenic processes that cancer cells adopt to metastasize. To the concept of uncontrolled proliferation of transformed cells, our proposed definition then adds "subject to evolution by natural selection." The subject to evolution by natural selection modernizes the definition to include the genetic and epigenetic changes that accumulate within a population of cancer cells that lead to the lethal phenotype. Cancer is a disease of uncontrolled proliferation by transformed cells subject to evolution by natural selection.
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10.
  • Bukkuri, Anuraag, et al. (författare)
  • A life history model of the ecological and evolutionary dynamics of polyaneuploid cancer cells
  • 2022
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Therapeutic resistance is one of the main reasons for treatment failure in cancer patients. The polyaneuploid cancer cell (PACC) state has been shown to promote resistance by providing a refuge for cancer cells from the effects of therapy and by helping them adapt to a variety of environmental stressors. This state is the result of aneuploid cancer cells undergoing whole genome doubling and skipping mitosis, cytokinesis, or both. In this paper, we create a novel mathematical framework for modeling the eco-evolutionary dynamics of state-structured populations and use this framework to construct a model of cancer populations with an aneuploid and a PACC state. Using in silico simulations, we explore how the PACC state allows cancer cells to (1) survive extreme environmental conditions by exiting the cell cycle after S phase and protecting genomic material and (2) aid in adaptation to environmental stressors by increasing the cancer cell’s ability to generate heritable variation (evolvability) through the increase in genomic content that accompanies polyploidization. In doing so, we demonstrate the ability of the PACC state to allow cancer cells to persist under therapy and evolve therapeutic resistance. By eliminating cells in the PACC state through appropriately-timed PACC-targeted therapies, we show how we can prevent the emergence of resistance and promote cancer eradication.
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11.
  • Bukkuri, Anuraag, et al. (författare)
  • A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations
  • 2023
  • Ingår i: Scientific Reports. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The polyaneuploid cancer cell (PACC) state promotes cancer lethality by contributing to survival in extreme conditions and metastasis. Recent experimental evidence suggests that post-therapy PACC-derived recurrent populations display cross-resistance to classes of therapies with independent mechanisms of action. We hypothesize that this can occur through PACC memory, whereby cancer cells that have undergone a polyaneuploid transition (PAT) reenter the PACC state more quickly or have higher levels of innate resistance. In this paper, we build on our prior mathematical models of the eco-evolutionary dynamics of cells in the 2N+ and PACC states to investigate these two hypotheses. We show that although an increase in innate resistance is more effective at promoting cross-resistance, this trend can also be produced via PACC memory. We also find that resensitization of cells that acquire increased innate resistance through the PAT have a considerable impact on eco-evolutionary dynamics and extinction probabilities. This study, though theoretical in nature, can help inspire future experimentation to tease apart hypotheses surrounding how cross-resistance in structured cancer populations arises.
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12.
  • Bukkuri, Anuraag, et al. (författare)
  • Modeling cancer’s ecological and evolutionary dynamics
  • 2023
  • Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 40:4
  • Tidskriftsartikel (refereegranskat)abstract
    • In this didactic paper, we present a theoretical modeling framework, called the G-function, that integrates both the ecology and evolution of cancer to understand oncogenesis. The G-function has been used in evolutionary ecology, but has not been widely applied to problems in cancer. Here, we build the G-function framework from fundamental Darwinian principles and discuss how cancer can be seen through the lens of ecology, evolution, and game theory. We begin with a simple model of cancer growth and add on components of cancer cell competition and drug resistance. To aid in exploration of eco-evolutionary modeling with this approach, we also present a user-friendly software tool. By the end of this paper, we hope that readers will be able to construct basic G function models and grasp the usefulness of the framework to understand the games cancer plays in a biologically mechanistic fashion.
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13.
  • Bukkuri, Anuraag, et al. (författare)
  • Stochastic models of Mendelian and reverse transcriptional inheritance in state-structured cancer populations
  • 2022
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent evidence suggests that a polyaneuploid cancer cell (PACC) state may play a key role in the adaptation of cancer cells to stressful environments and in promoting therapeutic resistance. The PACC state allows cancer cells to pause cell division and to avoid DNA damage and programmed cell death. Transition to the PACC state may also lead to an increase in the cancer cell’s ability to generate heritable variation (evolvability). One way this can occur is through evolutionary triage. Under this framework, cells gradually gain resistance by scaling hills on a fitness landscape through a process of mutation and selection. Another way this can happen is through self-genetic modification whereby cells in the PACC state find a viable solution to the stressor and then undergo depolyploidization, passing it on to their heritably resistant progeny. Here, we develop a stochastic model to simulate both of these evolutionary frameworks. We examine the impact of treatment dosage and extent of self-genetic modification on eco-evolutionary dynamics of cancer cells with aneuploid and PACC states. We find that under low doses of therapy, evolutionary triage performs better whereas under high doses of therapy, self-genetic modification is favored. This study generates predictions for teasing apart these biological hypotheses, examines the implications of each in the context of cancer, and provides a modeling framework to compare Mendelian and non-traditional forms of inheritance.
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14.
  • Bukkuri, Anuraag, et al. (författare)
  • The contribution of evolvability to the eco-evolutionary dynamics of competing species
  • 2023
  • Ingår i: Ecology and Evolution. - 2045-7758. ; 13:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Evolvability is the capacity of a population to generate heritable variation that can be acted upon by natural selection. This ability influences the adaptations and fitness of individual organisms. By viewing this capacity as a trait, evolvability is subject to natural selection and thus plays a critical role in eco-evolutionary dynamics. Understanding this role provides insight into how species respond to changes in their environment and how species coexistence can arise and be maintained. Here, we create a G-function model of competing species, each with a different evolvability. We analyze population and strategy (= heritable phenotype) dynamics of the two populations under clade initiation (when species are introduced into a population), evolutionary tracking (constant, small changes in the environment), adaptive radiation (availability of multiple ecological niches), and evolutionary rescue (extreme environmental disturbances). We find that when species are far from an eco-evolutionary equilibrium, faster-evolving species reach higher population sizes, and when species are close to an equilibrium, slower-evolving species are more successful. Frequent, minor environmental changes promote the extinction of species with small population sizes, regardless of their evolvability. When several niches are available for a species to occupy, coexistence is possible, though slower-evolving species perform slightly better than faster-evolving ones due to the well-recognized inherent cost of evolvability. Finally, disrupting the environment at intermediate frequencies can result in coexistence with cyclical population dynamics of species with different rates of evolution.
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15.
  • Dahl, Tais W., et al. (författare)
  • Devonian rise in atmospheric oxygen correlated to the radiations of terrestrial plants and large predatory fish
  • 2010
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:42, s. 17911-17915
  • Tidskriftsartikel (refereegranskat)abstract
    • The evolution of Earth's biota is intimately linked to the oxygenation of the oceans and atmosphere. We use the isotopic composition and concentration of molybdenum (Mo) in sedimentary rocks to explore this relationship. Our results indicate two episodes of global ocean oxygenation. The first coincides with the emergence of the Ediacaran fauna, including large, motile bilaterian animals, ca. 550-560 million year ago (Ma), reinforcing previous geochemical indications that Earth surface oxygenation facilitated this radiation. The second, perhaps larger, oxygenation took place around 400 Ma, well after the initial rise of animals and, therefore, suggesting that early metazoans evolved in a relatively low oxygen environment. This later oxygenation correlates with the diversification of vascular plants, which likely contributed to increased oxygenation through the enhanced burial of organic carbon in sediments. It also correlates with a pronounced radiation of large predatory fish, animals with high oxygen demand. We thereby couple the redox history of the atmosphere and oceans to major events in animal evolution.
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16.
  • Dahl, Tais W., et al. (författare)
  • Do large predatory fish track ocean oxygenation?
  • 2011
  • Ingår i: Communicative & Integrative Biology. - : Informa UK Limited. - 1942-0889. ; 4:1, s. 92-94
  • Tidskriftsartikel (refereegranskat)abstract
    • The Devonian appearance of 1-10 meter long armored fish (placoderms) coincides with geochemical evidence recording a transition into fully oxygenated oceans. A comparison of extant fish shows that the large individuals are less tolerant to hypoxia than their smaller cousins. This leads us to hypothesize that Early Paleozoic O2 saturation levels were too low to support >1 meter size marine, predatory fish. According to a simple model, both oxygen uptake and oxygen demand scale positively with size, but the demand exceeds supply for the largest fish with an active, predatory life style. Therefore, the largest individuals may lead us to a lower limit on oceanic O2 concentrations. Our presented model suggests 2-10 meter long predators require >30-50% PAL while smaller fish would survive at <25% PAL. This is consistent with the hypothesis that low atmospheric oxygen pressure acted as an evolutionary barrier for fish to grow much above ~1 meter before the Devonian oxygenation. 
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17.
  • Dahl, Tais W., et al. (författare)
  • Reply to Butterfield : The Devonian radiation of large predatory fish coincided with elevated athospheric oxygen levels
  • 2011
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:9, s. E29-
  • Tidskriftsartikel (refereegranskat)abstract
    • We welcome this opportunity to clarify the conclusions and implications of our recent publication in PNAS. Butterfield (1) raises four issues regarding the oxygenation of the Paleozoic Earth's surface and its correlation to animal evolution. Our geochemical and paleontological data supported ocean oxygenation in the Silurian-Early Devonian (2), a critical transition in Earth history that influenced biogeochemical cycles and biological systems. First, Butterfield suggests that evidence of charcoal in late Silurian rocks is incompatible with our claim that the earlier Paleozoic atmosphere had oxygen levels below 50% PAL (present-day atmospheric level). This counterargument rests on the assumption that the “fire window” of 62–166% PAL oxygen is well defined, but this is not the case (3).
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18.
  • Dahl, Tais W., et al. (författare)
  • Sulfidic anoxia in the oceans during the Late Ordovician mass extinctions – insights from molybdenum and uranium isotopic global redox proxies
  • 2021
  • Ingår i: Earth-Science Reviews. - : Elsevier BV. - 0012-8252. ; 220
  • Forskningsöversikt (refereegranskat)abstract
    • The Late Ordovician Mass Extinction wiped out 85% of animal species in two phases (LOME1 and LOME2). The kill mechanisms for the extinction phases are debated, but deteriorating climate and the expansion of marine anoxia appear to have been important factors. Nevertheless, the spatial extent and intensity of marine anoxia and its temporal relationship with the extinctions are not well understood. Here, we review existing global paleoredox proxy data based on molybdenum (Mo) and uranium (U) isotopes from four paleocontinents combined with new Mo isotope data from Dob's Linn, Scotland. Individually, these sedimentary records demonstrate significant redox fluctuations, but our coupled dynamic oceanic mass balance model for the evolution of the marine Mo and U cycles reveals that globally expansive ocean anoxia is best constrained by δ238U in carbonates from Anticosti Island that record expansive anoxia during LOME2. In addition, we consider periodic sulfidic anoxia developing in well-ventilated parts of the shallow oceans (e.g. during warmer periods with greater solar insolation) to have produced temporarily high seawater δ98Mo values during LOME1 in accordance with trends to high values observed in the sedimentary records. In this view, oceanic oxygen loss had a causal role during both extinction phases in the Late Ordovician.
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19.
  • El Albani, Abderrazak, et al. (författare)
  • Large colonial organisms with coordinated growth in oxygenated environments 2.1 Gyr ago
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7302, s. 100-104
  • Tidskriftsartikel (refereegranskat)abstract
    • The evidence for macroscopic life during the Palaeoproterozoic era (2.5-1.6 Gyr ago) is controversial(1-5). Except for the nearly 2-Gyr-old coil-shaped fossil Grypania spiralis(6,7), which may have been eukaryotic, evidence for morphological and taxonomic bio-diversification of macroorganisms only occurs towards the beginning of the Mesoproterozoic era (1.6-1.0 Gyr)(8). Here we report the discovery of centimetre-sized structures from the 2.1-Gyr-old black shales of the Palaeoproterozoic Francevillian B Formation in Gabon, which we interpret as highly organized and spatially discrete populations of colonial organisms. The structures are up to 12 cm in size and have characteristic shapes, with a simple but distinct ground pattern of flexible sheets and, usually, a permeating radial fabric. Geochemical analyses suggest that the sediments were deposited under an oxygenated water column. Carbon and sulphur isotopic data indicate that the structures were distinct biogenic objects, fossilized by pyritization early in the formation of the rock. The growth patterns deduced from the fossil morphologies suggest that the organisms showed cell-to-cell signalling and coordinated responses, as is commonly associated with multicellular organization(9). The Gabon fossils, occurring after the 2.45-2.32-Gyr increase in atmospheric oxygen concentration(10), may be seen as ancient representatives of multicellular life, which expanded so rapidly 1.5 Gyr later, in the Cambrian explosion.
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20.
  • Gaines, Robert R., et al. (författare)
  • Mechanism for Burgess Shale-type preservation
  • 2012
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:14, s. 5180-5184
  • Tidskriftsartikel (refereegranskat)abstract
    • Exceptionally preserved fossil biotas of the Burgess Shale and a handful of other similar Cambrian deposits provide rare but critical insights into the early diversification of animals. The extraordinary preservation of labile tissues in these geographically widespread but temporally restricted soft-bodied fossil assemblages has remained enigmatic since Walcott’s initial discovery in 1909. Here, we demonstrate the mechanism of Burgess Shale-type preservation using sedimentologic and geochemical data from the Chengjiang, Burgess Shale, and five other principal Burgess Shale-type deposits. Sulfur isotope evidence from sedimentary pyrites reveals that the exquisite fossilization of organic remains as carbonaceous compressions resulted from early inhibition of microbial activity in the sediments by means of oxidant deprivation. Low sulfate concentrations in the global ocean and low-oxygen bottom water conditions at the sites of deposition resulted in reduced oxidant availability. Subsequently, rapid entombment of fossils in fine-grained sediments and early sealing of sediments by pervasive carbonate cements at bed tops restricted oxidant flux into the sediments. A permeability barrier, provided by bed-capping cements that were emplaced at the seafloor, is a feature that is shared among Burgess Shale-type deposits, and resulted from the unusually high alkalinity of Cambrian oceans. Thus, Burgess Shale-type preservation of soft-bodied fossil assemblages worldwide was promoted by unique aspects of early Paleozoic seawater chemistry that strongly impacted sediment diagenesis, providing a fundamentally unique record of the immediate aftermath of the “Cambrian explosion.”
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21.
  • Gatenby, Robert A., et al. (författare)
  • Lung adenocarcinomas without driver genes converge to common adaptive strategies through diverse genetic, epigenetic, and niche construction evolutionary pathways
  • 2024
  • Ingår i: Medical Oncology. - 1357-0560. ; 41:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Somatic evolution selects cancer cell phenotypes that maximize survival and proliferation in dynamic environments. Although cancer cells are molecularly heterogeneous, we hypothesized convergent adaptive strategies to common host selection forces can be inferred from patterns of epigenetic and genetic evolutionary selection in similar tumors. We systematically investigated gene mutations and expression changes in lung adenocarcinomas with no common driver genes (n = 313). Although 13,461 genes were mutated in at least one sample, only 376 non-synonymous mutations evidenced positive evolutionary selection with conservation of 224 genes, while 1736 and 2430 genes exhibited ≥ two-fold increased and ≥ 50% decreased expression, respectively. Mutations under positive selection are more frequent in genes with significantly altered expression suggesting they often “hardwire” pre-existing epigenetically driven adaptations. Conserved genes averaged 16-fold higher expression in normal lung tissue compared to those with selected mutations demonstrating pathways necessary for both normal cell function and optimal cancer cell fitness. The convergent LUAD phenotype exhibits loss of differentiated functions and cell–cell interactions governing tissue organization. Conservation with increased expression is found in genes associated with cell cycle, DNA repair, p53 pathway, epigenetic modifiers, and glucose metabolism. No canonical driver gene pathways exhibit strong positive selection, but extensive down-regulation of membrane ion channels suggests decreased transmembrane potential may generate persistent proliferative signals. NCD LUADs perform niche construction generating a stiff, immunosuppressive microenvironment through selection of specific collagens and proteases. NCD LUADs evolve to a convergent phenotype through a network of interconnected genetic, epigenetic, and ecological pathways.
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22.
  • Gill, Benjamin C., et al. (författare)
  • Redox dynamics of later Cambrian oceans
  • 2021
  • Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182. ; 581
  • Tidskriftsartikel (refereegranskat)abstract
    • A growing body of evidence suggests that the deep oceans during the early Paleozoic Era were widely oxygen deficient, despite evidence for increased marine oxygenation during the Neoproterozoic. However, the temporal and geographic extents and dynamics of reducing marine conditions within these oceans are not well understood. Here, we investigate marine redox history during the Drumian through the earliest Jiangshanian International Stages of the Cambrian Period, using concentrations of redox-sensitive metals (vanadium, uranium, and molybdenum), iron speciation, and Mo isotope stratigraphy of the Alum Shale Formation of Scandinavia. These data suggest a major perturbation occurred in trace metal cycling during the later Cambrian Period that was linked to a transient change in marine redox conditions coincident with the well-known Steptoean Positive Isotope Excursion or SPICE. The δ98Mo measurements of the Alum shale show systematic variations during the interval that contains the SPICE which are broadly consistent with a transient expansion of sulfidic, reducing marine environments — indicating a significant exacerbation of an already-common condition during the Cambrian Period. Additionally, iron speciation data record a local transition from predominantly anoxic, ferruginous (Fe+2 containing) to anoxic, euxinic (sulfide containing) water column conditions near the initiation of the SPICE. Trace metal abundances, however, appear to decline well before the start of the SPICE, suggesting an earlier initiation of the global expansion of reducing environments. More broadly, our data and modeling support the notion that significant portions of the oceans remained oxygen deficient throughout the later portion of the Cambrian, and that these oceans were also prone to transient intervals of more reducing conditions similar to the Oceanic Anoxic Events of the Mesozoic.
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23.
  • Hammarlund, Emma U., 1971-, et al. (författare)
  • A sulfidic driver for the end-Ordovician mass extinction
  • 2012
  • Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 331, s. 128-139
  • Tidskriftsartikel (refereegranskat)abstract
    • The end-Ordovician extinction consisted of two discrete pulses, both linked, in various ways, to glaciation at the South Pole. The first phase, starting just below the Normalograptus extraordinarius Zone, particularly affected nektonic and planktonic species, while the second pulse, associated with the Normalograptus persculptus Zone, was less selective. Glacially induced cooling and oxygenation are two of many suggested kill mechanisms for the end-Ordovician extinction, but a general consensus is lacking. We have used geochemical redox indicators, such as iron speciation, molybdenum concentrations, pyrite framboid size distribution and sulfur isotopes to analyze the geochemistry in three key Hirnantian sections. These indicators reveal that reducing conditions were occasionally present at all three sites before the first pulse of the end-Ordovician extinction, and that these conditions expanded towards the second pulse. Even though the N. extraordinarius Zone appears to have been a time of oxygenated deposition, pyrite is significantly enriched in 34S in our sections as well as in sections reported from South China. This suggests a widespread reduction in marine sulfate concentrations, which we attribute to an increase in pyrite burial during the early Hirnantian. The S-isotope excursion coincides with a major positive carbon isotope excursion indicating elevated rates of organic carbon burial as well. We argue that euxinic conditions prevailed and intensified in the early Hirnantian oceans, and that a concomitant global sea level lowering pushed the chemocline deeper than the depositional setting of our sites. In the N. persculptus Zone, an interval associated with a major sea level rise, our redox indicators suggests that euxinic conditions, and ferruginous in some places, encroached onto the continental shelves. In our model, the expansion of euxinic conditions during the N. extraordinarius Zone was generated by a reorganization of nutrient cycling during sea level fall, and we argue, overall, that these dynamics in ocean chemistry played an important role for the end-Ordovician mass extinction. During the first pulse of the extinction, euxinia and a steepened oxygen gradient in the water column caused habitat loss for deep-water benthic and nektonic organisms. During the second pulse, the transgression of anoxic water onto the continental shelves caused extinction in shallower habitats.
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24.
  • Hammarlund, Emma U., et al. (författare)
  • Early Cambrian oxygen minimum zone-like conditions at Chengjiang
  • 2017
  • Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X. ; 475, s. 160-168
  • Tidskriftsartikel (refereegranskat)abstract
    • The early Cambrian succession at Chengjiang contains the most diverse Cambrian fossil assemblage yet described, and contributes significantly to our understanding of the diversification of metazoans in the Cambrian “explosion”. The Cambrian Period occupies a transitional episode of global ocean chemistry, following the oxygenation of the surface ocean and of shallow marine environments during the Ediacaran Period, but prior to the establishment of a predominantly oxygenated deep ocean in the mid-Paleozoic. Despite recent attention, a detailed understanding of the chemical conditions that prevailed in early Cambrian marine settings and the relationship of those conditions to early metazoan ecosystems is still emerging. Here, we report multi-proxy geochemical data from two drill cores through the early Cambrian (Series 2) Yu'anshan Formation of Yunnan, China. Results reveal dynamic water-column chemistry within the succession, which progressively shifted from euxinic to oxic conditions during deposition of the Yu'anshan Formation. The Chengjiang biota occurs in strata that appear to have been deposited under an oxygen-depleted water column that may have supported denitrification, as in modern oxygen-minimum zones. The oxygenated benthic environments in which the Chengjiang biota thrived were proximal to, but sharply separated from, the open ocean by a persistent anoxic water mass that occupied a portion of the outer shelf. Oxygen depletion in the lower water column developed dynamically in response to nutrient availability and possibly at lower thresholds of productivity due to lower atmospheric oxygen concentrations in Cambrian. These findings suggest that the frequent development of oxygen-limiting conditions in continental margin settings provided an environmental barrier that may have affected biogeographic, ecological and evolutionary development of early metazoan communities.
  •  
25.
  • Hammarlund, Emma U., et al. (författare)
  • Early Silurian δ 13 C org excursions in the foreland basin of Baltica, both familiar and surprising
  • 2019
  • Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182. ; 526, s. 126-135
  • Tidskriftsartikel (refereegranskat)abstract
    • The Sommerodde-1 core from Bornholm, Denmark, provides a nearly continuous sedimentary archive from the Upper Ordovician through to the Wenlock Series (lower Silurian), as constrained by graptolite biostratigraphy. The cored mudstones represent a deep marine depositional setting in the foreland basin fringing Baltica and we present high-resolution data on the isotopic composition of the section's organic carbon (δ 13 C org ). This chemostratigraphical record is correlated with previously recognized δ 13 C excursions in the Upper Ordovician–lower Silurian, including the Hirnantian positive isotope carbon excursion (HICE), the early Aeronian positive carbon isotope excursion (EACIE), and the early Sheinwoodian positive carbon isotope excursion (ESCIE). A new positive excursion of high magnitude (~4‰)is discovered in the Telychian Oktavites spiralis Biozone (lower Silurian)and we name it the Sommerodde Carbon Isotope Excursion (SOCIE). The SOCIE appears discernible in δ 13 C carb data from Latvian and Estonian cores but it is not yet widely recognized. However, the magnitude of the excursion within the deep, marine, depositional setting, represented by the Sommerodde-1 core, suggests that the SOCIE reflects a significant event. In addition, the chemostratigraphical record of the Sommerodde-1 core reveals the negative excursion at the transition from the Aeronian to Telychian stages (the ‘Rumba low’), and suggests that the commencement of the EACIE at the base of the Demirastrites triangulatus Biozone potentially is a useful chemostratigraphical marker for the base of the Aeronian Stage.
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26.
  • Hammarlund, Emma U. (författare)
  • Harnessing hypoxia as an evolutionary driver of complex multicellularity : Hypoxia drives multicellular evolution
  • 2020
  • Ingår i: Interface Focus. - 2042-8898. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Animal tissue requires low-oxygen conditions for its maintenance. The need for low-oxygen conditions contrasts with the idea of an evolutionary leap in animal diversity as a result of expanding oxic conditions. To accommodate tissue renewal at oxic conditions, however, vertebrate animals and vascular plants demonstrate abilities to access hypoxia. Here, I argue that multicellular organisms sustain oxic conditions first after internalizing hypoxic conditions. The 'harnessing' of hypoxia has allowed multicellular evolution to leave niches that were stable in terms of oxygen concentrations for those where oxygen fluctuates. Since oxygen fluctuates in most settings on Earth's surface, the ancestral niche would have been a deep marine setting. The hypothesis that 'large life' depends on harnessing hypoxia is illustrated in the context of conditions that promote the immature cell phenotype (stemness) in animal physiology and tumour biology and offers one explanation for the general rarity of diverse multicellularity over most of Earth's history.
  •  
27.
  • Hammarlund, Emma U., 1971- (författare)
  • Ocean chemistry and the evolution of multicellularity
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Oxygen has been assumed to be a vital trigger for the evolution of multicellular life forms on Earth, partly based on its power to promote substantial energy flux in cell respiration and partly as biosynthesis of compounds like collagen require oxygen. However, the co-evolution of large life and the Earth’s chemical environment is not well understood at present, and there is particular disagreement in the field about whether the Cambrian explosion of animal life forms was a chemical or biological event. Here, I discuss the evolution of multicellularity, divided in simple or complex forms, in light of the evolution of ocean water column chemistry in both the Proterozoic and the early Paleozoic. Even if the appearance of animals is confined to the Ediacaran, other fossil evidence of complex multicellularity can be argued to occur in the Paleo-, Meso- and Neoproterozic. These finds are, if anything, reason enough to keep searching for early experiments in complex multicellularity. In this search, we may have to expand our toolbox by looking at e.g. trace element aggregations and the isotopic composition of key elements.  Research over the last couple of years have accentuated that much of the interval between the Ediacaran and the Devonian was dramatic with transitional ocean chemistry at the same time that large forms of animal life experienced dynamic radiation and ecological expansion. Results presented here describe some aspects of this time, including geochemistry from Chengjiang and a mechanism for preserving non-mineralized Cambrian animals that was partly dependent on specific ocean chemistry. Also, geochemical proxies using iron and molybdenum are used to infer a Paleozoic atmosphere with less than 50% of present levels of oxygen. The possibility that the subsequent rise is due to terrestrial plants and linked to the appearance of large predatory fish is discussed. Finally, the first mass extinction in the end-Ordovician is linked to low oxygen concentrations in the water column. It appears that more than oxygen was critical to allow the radiation of large life forms on Earth, but that chemistry and tectonic activity were intimately intertwined to biology, in a dance of permitting and being determined by certain aspects of ecology.
  •  
28.
  • Hammarlund, Emma U., et al. (författare)
  • Oxygen-sensing mechanisms across eukaryotic kingdoms and their roles in complex multicellularity
  • 2020
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 370:6515
  • Forskningsöversikt (refereegranskat)abstract
    • Oxygen-sensing mechanisms of eukaryotic multicellular organisms coordinate hypoxic cellular responses in a spatiotemporal manner. Although this capacity partly allows animals and plants to acutely adapt to oxygen deprivation, its functional and historical roots in hypoxia emphasize a broader evolutionary role. For multicellular life-forms that persist in settings with variable oxygen concentrations, the capacity to perceive and modulate responses in and between cells is pivotal. Animals and higher plants represent the most complex life-forms that ever diversified on Earth, and their oxygen-sensing mechanisms demonstrate convergent evolution from a functional perspective. Exploring oxygen-sensing mechanisms across eukaryotic kingdoms can inform us on biological innovations to harness ever-changing oxygen availability at the dawn of complex life and its utilization for their organismal development.
  •  
29.
  • Hammarlund, Emma U., et al. (författare)
  • Refined control of cell stemness allowed animal evolution in the oxic realm
  • 2018
  • Ingår i: Nature Ecology and Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:2, s. 220-228
  • Forskningsöversikt (refereegranskat)abstract
    • Animal diversification on Earth has long been presumed to be associated with the increasing extent of oxic niches. Here, we challenge that view. We start with the fact that hypoxia (<1-3% O2) maintains cellular immaturity (stemness), whereas adult stem cells continuously - and paradoxically - regenerate animal tissue in oxygenated settings. Novel insights from tumour biology illuminate how cell stemness nevertheless can be achieved through the action of oxygen-sensing transcription factors in oxygenated, regenerating tissue. We suggest that these hypoxia-inducible transcription factors provided animals with unprecedented control over cell stemness that allowed them to cope with fluctuating oxygen concentrations. Thus, a refinement of the cellular hypoxia-response machinery enabled cell stemness at oxic conditions and, then, animals to evolve into the oxic realm. This view on the onset of animal diversification is consistent with geological evidence and provides a new perspective on the challenges and evolution of multicellular life.
  •  
30.
  • Hammarlund, Emma U., et al. (författare)
  • The issues with tissues : the wide range of cell fate separation enables the evolution of multicellularity and cancer
  • 2020
  • Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 37:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Our understanding of the rises of animal and cancer multicellularity face the same conceptual hurdles: what makes the clade originate and what makes it diversify. Between the events of origination and diversification lies complex tissue organization that gave rise to novel functionality for organisms and, unfortunately, for malignant transformation in cells. Tissue specialization with distinctly separated cell fates allowed novel functionality at organism level, such as for vertebrate animals, but also involved trade-offs at the cellular level that are potentially disruptive. These trade-offs are under-appreciated and here we discuss how the wide separation of cell phenotypes may contribute to cancer evolution by (a) how factors can reverse differentiated cells into a window of phenotypic plasticity, (b) the reversal to phenotypic plasticity coupled with asexual reproduction occurs in a way that the host cannot adapt, and (c) the power of the transformation factor correlates to the power needed to reverse tissue specialization. The role of reversed cell fate separation for cancer evolution is strengthened by how some tissues and organisms maintain high cell proliferation and plasticity without developing tumours at a corresponding rate. This demonstrates a potential proliferation paradox that requires further explanation. These insights from the cancer field, which observes tissue evolution in real time and closer than any other field, allow inferences to be made on evolutionary events in animal history. If a sweet spot of phenotypic and reproductive versatility is key to transformation, factors stimulating cell fate separation may have promoted also animal diversification on Earth.
  •  
31.
  • Hammarlund, Emma U., et al. (författare)
  • The Sirius Passet Lagerstätte of North Greenland—A geochemical window on early Cambrian low-oxygen environments and ecosystems
  • 2019
  • Ingår i: Geobiology. - : Wiley. - 1472-4677. ; 17:1, s. 12-26
  • Tidskriftsartikel (refereegranskat)abstract
    • The early Cambrian Sirius Passet fauna of northernmost Greenland (Cambrian Series 2, Stage 3) contains exceptionally preserved soft tissues that provide an important window to early animal evolution, while the surrounding sediment holds critical data on the palaeodepositional water-column chemistry. The present study combines palaeontological data with a multiproxy geochemical approach based on samples collected in situ at high stratigraphic resolution from Sirius Passet. After careful consideration of chemical alterations during burial, our results demonstrate that fossil preservation and biodiversity show significant correlation with iron enrichments (FeHR/FeT), trace metal behaviour (V/Al), and changes in nitrogen cycling (δ15N). These data, together with Mo/Al and the preservation of organic carbon (TOC), are consistent with a water column that was transiently low in oxygen concentration, or even intermittently anoxic. When compared with the biogeochemical characteristics of modern oxygen minimum zones (OMZs), geochemical and palaeontological data collectively suggest that oxygen concentrations as low as 0.2–0.4 ml/L restricted bioturbation but not the development of a largely nektobenthic community of predators and scavengers. We envisage for the Sirius Passet biota a depositional setting where anoxic water column conditions developed and passed over the depositional site, possibly in association with sea-level change, and where this early Cambrian biota was established in conditions with very low oxygen.
  •  
32.
  • Harper, David A.T., et al. (författare)
  • The Sirius Passet Lagerstätte of North Greenland: a remote window on the Cambrian Explosion
  • 2019
  • Ingår i: Journal of the Geological Society. - : Geological Society of London. - 0016-7649 .- 2041-479X. ; 176, s. 1023-1037
  • Tidskriftsartikel (refereegranskat)abstract
    • The lower Cambrian Lagerstätte of Sirius Passet, Peary Land, North Greenland, is one of the oldest of the Phanerozoic exceptionally preserved biotas. The Lagerstätte evidences the escalation of numbers of new body plans and life modes that formed the basis for a modern, functionally tiered ecosystem. The fauna is dominated by predators, infaunal, benthic and pelagic, and the presence of abundant nekton, including large sweep-net feeders, suggests an ecosystem rich in nutrients. Recent discoveries have helped reconstruct digestive systems and their contents, muscle fibres, and visual and nervous systems for a number of taxa. New collections have confirmed the complex combination of taphonomic pathways associated with the biota and its potentially substantial biodiversity. These complex animal-based communities within the Buen Formation were associated with microbial matgrounds, now preserved in black mudstones deposited below storm wave base that provide insight into the shift from late Neoproterozoic (Ediacaran) to Cambrian substrates and communities. Moreover, the encasing sediment holds important data on the palaeoenvironment and the water-column chemistry, suggesting that these animal-based communities developed in conditions with very low oxygen concentrations.
  •  
33.
  • Jacques, Florian, et al. (författare)
  • Origin and evolution of animal multicellularity in the light of phylogenomics and cancer genetics
  • 2022
  • Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 39:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The rise of animals represents a major but enigmatic event in the evolutionary history of life. In recent years, numerous studies have aimed at understanding the genetic basis of this transition. However, genome comparisons of diverse animal and protist lineages suggest that the appearance of gene families that were previously considered animal specific indeed preceded animals. Animals’ unicellular relatives, such as choanoflagellates, ichthyosporeans, and filastereans, demonstrate complex life cycles including transient multicellularity as well as genetic toolkits for temporal cell differentiation, cell-to-cell communication, apoptosis, and cell adhesion. This has warranted further exploration of the genetic basis underlying transitions in cellular organization. An alternative model for the study of transitions in cellular organization is tumors, which exploit physiological programs that characterize both unicellularity and multicellularity. Tumor cells, for example, switch adhesion on and off, up- or downregulate specific cell differentiation states, downregulate apoptosis, and allow cell migration within tissues. Here, we use insights from both the fields of phylogenomics and tumor biology to review the evolutionary history of the regulatory systems of multicellularity and discuss their overlap. We claim that while evolutionary biology has contributed to an increased understanding of cancer, broad investigations into tissue—normal and transformed—can also contribute the framework for exploring animal evolution.
  •  
34.
  • Jacques, Florian, et al. (författare)
  • Roadmap to the study of gene and protein phylogeny and evolution—A practical guide
  • 2023
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Developments in sequencing technologies and the sequencing of an ever-increasing number of genomes have revolutionised studies of biodiversity and organismal evolution. This accumulation of data has been paralleled by the creation of numerous public biological databases through which the scientific community can mine the sequences and annotations of genomes, transcriptomes, and proteomes of multiple species. However, to find the appropriate databases and bioinformatic tools for respective inquiries and aims can be challenging. Here, we present a compilation of DNA and protein databases, as well as bioinformatic tools for phylogenetic reconstruction and a wide range of studies on molecular evolution. We provide a protocol for information extraction from biological databases and simple phylogenetic reconstruction using probabilistic and distance methods, facilitating the study of biodiversity and evolution at the molecular level for the broad scientific community.
  •  
35.
  • Kozik, Nevin P., et al. (författare)
  • Rapid marine oxygen variability : Driver of the Late Ordovician mass extinction
  • 2022
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:46
  • Tidskriftsartikel (refereegranskat)abstract
    • The timing and connections between global cooling, marine redox conditions, and biotic turnover are underconstrained for the Late Ordovician. The second most severe mass extinction occurred at the end of the Ordovician period, resulting in ~85% loss of marine species between two extinction pulses. As the only “Big 5” extinction that occurred during icehouse conditions, this interval is an important modern analog to constrain environmental feedbacks. We present a previously unexplored thallium isotope records from two paleobasins that record global marine redox conditions and document two distinct and rapid excursions suggesting vacillating (de)oxygenation. The strong temporal link between these perturbations and extinctions highlights the possibility that dynamic marine oxygen fluctuations, rather than persistent, stable global anoxia, played a major role in driving the extinction. This evidence for rapid oxygen changes leading to mass extinction has important implications for modern deoxygenation and biodiversity declines.
  •  
36.
  • Philipsen, Mai H., et al. (författare)
  • Distinct Cholesterol Localization in Glioblastoma Multiforme Revealed by Mass Spectrometry Imaging
  • 2023
  • Ingår i: ACS Chemical Neuroscience. - 1948-7193. ; 14:9, s. 1602-1609
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in adults and is highly resistant to chemo- and radiotherapies. GBM has been associated with alterations in lipid contents, but lipid metabolism reprogramming in tumor cells is not fully elucidated. One of the key hurdles is to localize the lipid species that are correlated with tumor growth and invasion. A better understanding of the localization of abnormal lipid metabolism and its vulnerabilities may open up to novel therapeutic approaches. Here, we use time-of-flight secondary ion mass spectrometry (ToF-SIMS) to spatially probe the lipid composition in a GBM biopsy from two regions with different histopathologies: one region with most cells of uniform size and shape, the homogeneous part, and the other with cells showing a great variation in size and shape, the heterogeneous part. Our results reveal elevated levels of cholesterol, diacylglycerols, and some phosphatidylethanolamine in the homogeneous part, while the heterogeneous part was dominated by a variety of fatty acids, phosphatidylcholine, and phosphatidylinositol species. We also observed a high expression of cholesterol in the homogeneous tumor region to be associated with large cells but not with macrophages. Our findings suggest that ToF-SIMS can distinguish in lipid distribution between parts within a human GBM tumor, which can be linked to different molecular mechanisms.
  •  
37.
  • Pienta, Kenneth J, et al. (författare)
  • Convergent Evolution, Evolving Evolvability, and the Origins of Lethal Cancer
  • 2020
  • Ingår i: Molecular cancer research : MCR. - 1557-3125. ; 18:6, s. 801-810
  • Forskningsöversikt (refereegranskat)abstract
    • Advances in curative treatment to remove the primary tumor have increased survival of localized cancers for most solid tumor types, yet cancers that have spread are typically incurable and account for >90% of cancer-related deaths. Metastatic disease remains incurable because, somehow, tumors evolve resistance to all known compounds, including therapies. In all of these incurable patients, de novo lethal cancer evolves capacities for both metastasis and resistance. Therefore, cancers in different patients appear to follow the same eco-evolutionary path that independently manifests in affected patients. This convergent outcome, that always includes the ability to metastasize and exhibit resistance, demands an explanation beyond the slow and steady accrual of stochastic mutations. The common denominator may be that cancer starts as a speciation event when a unicellular protist breaks away from its multicellular host and initiates a cancer clade within the patient. As the cancer cells speciate and diversify further, some evolve the capacity to evolve: evolvability. Evolvability becomes a heritable trait that influences the available variation of other phenotypes that can then be acted upon by natural selection. Evolving evolvability may be an adaptation for cancer cells. By generating and maintaining considerable heritable variation, the cancer clade can, with high certainty, serendipitously produce cells resistant to therapy and cells capable of metastasizing. Understanding that cancer cells can swiftly evolve responses to novel and varied stressors create opportunities for adaptive therapy, double-bind therapies, and extinction therapies; all involving strategic decision making that steers and anticipates the convergent coevolutionary responses of the cancers.
  •  
38.
  • Pienta, Kenneth J., et al. (författare)
  • Poly-aneuploid cancer cells promote evolvability, generating lethal cancer
  • 2020
  • Ingår i: Evolutionary Applications. - : Wiley. - 1752-4563 .- 1752-4571. ; 13:7, s. 1626-1634
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer cells utilize the forces of natural selection to evolve evolvability allowing a constant supply of heritable variation that permits a cancer species to evolutionary track changing hazards and opportunities. Over time, the dynamic tumor ecosystem is exposed to extreme, catastrophic changes in the conditions of the tumor—natural (e.g., loss of blood supply) or imposed (therapeutic). While the nature of these catastrophes may be varied or unique, their common property may be to doom the current cancer phenotype unless it evolves rapidly. Poly-aneuploid cancer cells (PACCs) may serve as efficient sources of heritable variation that allows cancer cells to evolve rapidly, speciate, evolutionarily track their environment, and most critically for patient outcome and survival, permit evolutionary rescue, therapy resistance, and metastasis. As a conditional evolutionary strategy, they permit the cancer cells to accelerate evolution under stress and slow down the generation of heritable variation when conditions are more favorable or when the cancer cells are closer to an evolutionary optimum. We hypothesize that they play a critical and outsized role in lethality by their increased capacity for invasion and motility, for enduring novel and stressful environments, and for generating heritable variation that can be dispensed to their 2N+ aneuploid progeny that make up the bulk of cancer cells within a tumor, providing population rescue in response to therapeutic stress. Targeting PACCs is essential to cancer therapy and patient cure—without the eradication of the resilient PACCs, cancer will recur in treated patients.
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