The Devonian appearance of 1-10 meter long armored fish (placoderms) coincides with geochemical evidence recording a transition into fully oxygenated oceans.
1
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 O
2
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 O
2
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.
The evidence for macroscopic life during the Palaeoproterozoic era (2.5-1.6Gyr ago) is controversial. Except for the nearly 2-Gyr-old coil-shaped fossil Grypania spiralis, which may have been ...eukaryotic, evidence for morphological and taxonomic biodiversification of macroorganisms only occurs towards the beginning of the Mesoproterozoic era (1.6-1.0Gyr). 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 12cm 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. The Gabon fossils, occurring after the 2.45-2.32-Gyr increase in atmospheric oxygen concentration, may be seen as ancient representatives of multicellular life, which expanded so rapidly 1.5Gyr later, in the Cambrian explosion.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Despite major advances in cancer research over the last several decades, advanced cancers largely remain incurable due to the evolution of resistance. Recent experimental evidence suggests ...that a poly-aneuploid cancer cell (PACC) state may contribute to the emergence of therapeutic resistance by allowing cancer cells to avoid the effects of and adapt to extreme environmental stressors. The PACC state is enabled when aneuploid cells undergo whole genome doubling but subsequently bypass mitosis, cytokinesis, or both. 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 evolvability (ability to generate heritable variation) through the increase in genomic content that accompanies polyploidization. In doing so, we demonstrate the ability of the PACC state to contribute to therapeutic resistance and stress the importance of targeting PACC populations for improved therapeutic outcomes.
Citation Format: Anuraag Bukkuri, Kenneth J. Pienta, Robert H. Austin, Emma U. Hammarlund, Sarah R. Amend, Joel S. Brown. Eco-evolutionary dynamics of poly-aneuploid cancer cells: A life history model abstract. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B015.
Abstract
We present a theoretical modeling framework, called the G function, to understand cancer speciation, diversification, and environmental adaptation. The G function integrates both the ecology ...and evolution of cancer and has been used in evolutionary ecology. However, the G function has not yet been widely applied to problems in cancer. Here, we build the G-function framework from fundamental Darwinian principles and discuss how cancer is inherently an evolutionary game. 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 online tool. We argue that G-functions are useful to understand the games cancer plays in a biologically mechanistic fashion.
Citation Format: Anuraag Bukkuri, Kenneth J. Pienta, Ian Hockett, Robert H. Austin, Emma U. Hammarlund, Sarah R. Amend, Joel S. Brown. Modeling cancer’s ecological and evolutionary dynamics abstract. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A001.
The Devonian appearance of 1–10 meter long armored fish (placoderms) coincides with geochemical evidence recording a transition into fully oxygenated oceans.
1
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 O
2
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 O
2
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.
Reply to Butterfield Dahl, Tais W.; Hammarlund, Emma U.; Anbar, Ariel D. ...
Proceedings of the National Academy of Sciences - PNAS,
2011, Letnik:
108, Številka:
9
Journal Article
Recenzirano
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).
The objective of this study was to evaluate the brain pharmacokinetic-pharmacodynamic relations of unbound oxycodone and morphine to investigate the influence of blood-brain barrier transport on ...differences in potency between these drugs.
Microdialysis was used to obtain unbound concentrations in brain and blood. The antinociceptive effect of each drug was assessed using the hot water tail-flick method. Population pharmacokinetic modeling was used to describe the blood-brain barrier transport of morphine as the rate (CLin) and extent (Kp,uu) of equilibration, where CLin is the influx clearance across the blood-brain barrier and Kp,uu is the ratio of the unbound concentration in brain to that in blood at steady state.
The six-fold difference in Kp,uu between oxycodone and morphine implies that, for the same unbound concentration in blood, the concentrations of unbound oxycodone in brain will be six times higher than those of morphine. A joint pharmacokinetic-pharmacodynamic model of oxycodone and morphine based on unbound brain concentrations was developed and used as a statistical tool to evaluate differences in the pharmacodynamic parameters of the drugs. A power model using Effect = Baseline + Slope . C best described the data. Drug-specific slope and gamma parameters made the relative potency of the drugs concentration dependent.
For centrally acting drugs such as opioids, pharmacokinetic-pharmacodynamic relations describing the interaction with the receptor are better obtained by correlating the effects to concentrations of unbound drug in the tissue of interest rather than to blood concentrations.
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.
Under lång tid har vi sett atmosfärens syrehalt som avgörande för att stora livsformer skulle börja utvecklas på jorden, delvis eftersom syre är ett energirikt bränsle men också för att det krävs vid sammansättningen av vissa ämnen som djur behöver, till exempel proteinet kollagen. Men, i själva verket, har vi inte lyckats reda ut detaljerna om hur utvecklingen av tidigt, stort liv och miljö satt samman, och om den kambriska explosionen framförallt var en biologisk eller kemiskt händelse. I den här avhandlingen diskuterar jag hur utvecklingen av flercellighet, då uppdelat i enkla och komplexa former, kan vara kopplad till hur havens kemi förändrats både i proterozoikum (2.5-0.5 miljarder år sedan) och paleozoikum (0.5-0 miljarder år sedan. Även om fossil från moderna djur dyker upp runt ediacaran och kambrium, så finns det långt äldre fossil som kan påvisa flercellighet. Dessa fossil ger, om inte annat, anledning att leta vidare efter fler spår av pre-kambrisk flercellighet och kanske kan vi utöka våra sökmetoder till att också tolka ansamlingar, eller isotopsammansättningar, av spårmetaller. Den kambriska explosinen av djurliv (med startskott för 543 miljoner år sedan) är ett etablerat begrepp, men den senaste årens forskning har satt fokus på att en längre period, från ediacaran till devon, var en dynamisk tid med skiftande havskemi, nya djurarter och experimentella ekologiska nätverk. I den här avhandlingen presenteras några resultat som belyser just denna övergångstid, som geokemin i Chengjiang som beskriver hur havets kemi skiftar från syrefritt till sulfatfritt till syrerikt, och hur djur utan skal och ben kunde bli bevarade genom att flera unika förhållanden sammanföll. En annan studie visar hur molybden använts för att påvisa att atmosfärens syrehalt, under den här perioden, var högst hälften av vår moderna nivå. Vi hävdar att stigningen som skedde i devon, delvis tack vare växternas intåg på land, och att stigningen kan speglas i att fiskar först då hade råd att jaga och växa sig stora. Slutligen visar jag också på hur det första stora massutdöendet kan vara sammankopplat med syrefria hav, snarare än kyla och mer syre än djuren klarade av. Ett komplext samspel mellan flera kemiska ämnen, utöver syre, tektonisk aktivitet och biologi ser ut att höra samman med den dramatiska uvecklingen för stora livsformer på jorden.
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