Multiple beds in the Frankfort Shale (Upper Ordovician, New York State), including the original "Beecher's Trilobite Bed," yield fossils with pyritized soft-tissues. A bed-by-bed geochemical and ...sedimentological analysis was carried out to test previous models of soft-tissue pyritization by investigating environmental, depositional and diagenetic conditions in beds with and without soft-tissue preservation. Highly-reactive iron (...), total iron (FeT), ..., organic carbon and redox-sensitive trace elements were measured. In particular, the partitioning of highly-reactive iron between iron-carbonates (Fe-carb), iron-oxides (Fe-ox), magnetite (Fe-mag), and pyrite (FeP) was examined. Overall, the multi-proxy sedimentary geochemical data suggest that the succession containing pyritized trilobite beds was deposited under a dysoxic water-column, in agreement with the paleontological data. The data do not exclude brief episodes of water-column anoxia characterized by a ferruginous rather than an euxinic state. However, the highest .../FeT values and redox-sensitive trace element enrichments occur in siltstone portions of turbidite beds and in concretions, suggesting that subsequent diagenesis had a significant effect on the distribution of redox-sensitive elements in this succession. Moderately high .../FeT and FeP/..., low organic carbon, enriched ? S, and the frequent presence of iron-rich carbonate concretions in beds with soft tissue preservation confirm that pyritization was favored where pore-waters were iron-dominated in sediments relatively poor in organic carbon. (ProQuest: ... denotes formulae/symbols omitted.)
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.
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.
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.
Prokaryotes, often generally referred to as “bacteria,” are the original and thus oldest life on Earth. They have shaped the chemical environment of the Earth, but they are difficult to find as ...ancient fossils due to their subtle structure. Here we report well-preserved fossilized microbial communities in silicified bitumen concretions from unit 3 of the Xiamaling Formation (1.39 Ga) in northern China. The numerous silicified bitumen concretions are in a variety of forms including ellipsoidal, spindle, and pancake ones, with diameters of 1~16 cm and thicknesses of 0.5~3 cm. The principal planes of the concretions are at low angle or directly parallel to the depositional plane level, showing obvious depositional characteristics. The concretions are silicified with abundant bitumen inside. Many different kinds of microbial fossils are found in the bitumen, including spherical forms, rods, and filaments, and some of the microbes are aggregated together in the forms of multicellular structures. These concretions preserve a delicate Mesoproterozoic biotic community.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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.
Therapeutic resistance and recurrence remain core challenges in cancer therapy. How therapy resistance arises is currently not fully understood with tumors surviving via multiple alternative routes. ...Here, we demonstrate that a subset of cancer cells survives therapeutic stress by entering a transient state characterized by whole-genome doubling. At the onset of the polyploidization program, we identified an upregulation of key transcriptional regulators, including the early stress-response protein AP-1 and normoxic stabilization of HIF2α. We found altered chromatin accessibility, ablated expression of retinoblastoma protein (RB1), and enrichment of AP-1 motif accessibility. We demonstrate that AP-1 and HIF2α regulate a therapy resilient and survivor phenotype in cancer cells. Consistent with this, genetic or pharmacologic targeting of AP-1 and HIF2α reduced the number of surviving cells following chemotherapy treatment. The role of AP-1 and HIF2α in stress response by polyploidy suggests a novel avenue for tackling chemotherapy-induced resistance in cancer.
In response to cisplatin treatment, some surviving cancer cells undergo whole-genome duplications without mitosis, which represents a mechanism of drug resistance. This study presents mechanistic data to implicate AP-1 and HIF2α signaling in the formation of this surviving cell phenotype. The results open a new avenue for targeting drug-resistant cells.
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.
Thallium isotopes reveal that rapid marine oxygen fluctuations in the Late Ordovician oceans are linked to mass extinction pulses.
We studied sediments from the ca. 1400 million-year-old Xiamaling Formation from the North China block. The upper unit of this formation (unit 1) deposited mostly below storm wave base and contains ...alternating black and green-gray shales with very distinct geochemical characteristics. The black shales are enriched in redox-sensitive trace metals, have high concentrations of total organic carbon (TOC), high hydrogen index (HI) and iron speciation indicating deposition under anoxic conditions. In contrast, the green-gray shales show no trace metal enrichments, have low TOC, low HI and iron speciation consistent with an oxygenated depositional setting. Altogether, unit 1 displays alternations between oxic and anoxic depositional environments, driving differences in carbon preservation consistent with observations from the modern ocean. We combined our TOC and HI results to calculate the differences in carbon mineralization and carbon preservation by comparing the oxygenated and anoxic depositional environments. Through comparisons of these results with modern sedimentary environments, and by use of a simple diagenetic model, we conclude that the enhanced carbon mineralization under oxygenated conditions in unit 1 of the Xiamaling Formation required a minimum of 4 to 8 % of present-day atmospheric levels (PAL) of oxygen. These oxygen levels are higher than estimates based on chromium isotopes and reinforce the idea that the environment contained enough oxygen for animals long before their evolution.
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