Geological and technological viewpoint on 3D Deposit Model – examples of use in Pniówek Coal Mine

During the more than 3 years of the “Quality” program at JSW S.A., a geological database has been built from scratch, collecting data from all exploratory boreholes, roadway profiling and the results of chemical analyses in one place – placing particular emphasis on parameters affecting the quality of coke. Working with digital databases requires new competencies for geologists – the ability to efficiently obtain information ready for further processing. As intended, the geological model became the basis for forecasting the quantity and quality of mined coal used in coke production. In the course of the work, a discrepancy became apparent between the geological interpretation of the structure of the deposit – as understood by the assumptions of the geological documentation, and the technological conditions of mining. The article presents resulting changes in the approach to modeling lithology and quality parameters. In addition, examples of the application of the geological database and the geological model in the daily work of the geological department are presented

Heat shock response regulates stimulus-specificity and sensitivity of the pro-inflammatory NF-κB signalling

From Springer Nature via Jisc Publications RouterHistory: received 2020-01-24, accepted 2020-04-16, registration 2020-04-16, pub-electronic 2020-05-24, online 2020-05-24, collection 2020-12Publication status: PublishedFunder: Narodowe Centrum Nauki; doi: http://dx.doi.org/10.13039/501100004281; Grant(s): 2016/23/B/ST6/03455, 2015/19/B/ST7/02984, 2016/21/B/ST7/02241Funder: Politechnika Śląska; doi: http://dx.doi.org/10.13039/501100007835; Grant(s): 02/010/BK19/0143Funder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/K003097/1Funder: Politechnika Poznańska; doi: http://dx.doi.org/10.13039/501100004239; Grant(s): 825/RN2/RR4/2018Abstract: Background: Ability to adapt to temperature changes trough the Heat Shock Response (HSR) pathways is one of the most fundamental and clinically relevant cellular response systems. Heat Shock (HS) affects the signalling and gene expression responses of the Nuclear Factor κB (NF-κB) transcription factor, a critical regulator of proliferation and inflammation, however, our quantitative understanding of how cells sense and adapt to temperature changes is limited. Methods: We used live-cell time-lapse microscopy and mathematical modelling to understand the signalling of the NF-κB system in the human MCF7 breast adenocarcinoma cells in response to pro-inflammatory Interleukin 1β (IL1β) and Tumour Necrosis Factor α (TNFα) cytokines, following exposure to a 37–43 °C range of physiological and clinical temperatures. Results: We show that exposure to 43 °C 1 h HS inhibits the immediate NF-κB signalling response to TNFα and IL1β stimulation although uptake of cytokines is not impaired. Within 4 h after HS treatment IL1β-induced NF-κB responses return to normal levels, but the recovery of the TNFα-induced responses is still affected. Using siRNA knock-down of Heat Shock Factor 1 (HSF1) we show that this stimulus-specificity is conferred via the Inhibitory κB kinase (IKK) signalosome where HSF1-dependent feedback regulates TNFα, but not IL1β-mediated IKK recovery post HS. Furthermore, we demonstrate that through the temperature-dependent denaturation and recovery of IKK, TNFα and IL1β-mediated signalling exhibit different temperature sensitivity and adaptation to repeated HS when exposed to a 37–43 °C temperature range. Specifically, IL1β-mediated NF-κB responses are more robust to temperature changes in comparison to those induced by TNFα treatment. Conclusions: We demonstrate that the kinetics of the NF-κB system following temperature stress is cytokine specific and exhibit differential adaptation to temperature changes. We propose that this differential temperature sensitivity is mediated via the IKK signalosome, which acts as a bona fide temperature sensor trough the HSR cross-talk. This novel quantitative understanding of NF-κB and HSR interactions is fundamentally important for the potential optimization of therapeutic hyperthermia protocols. D-ESB-DSZSgbr1c4s2oumkVideo Abstrac

Inferring genomic duplication events

One of evolutionary molecular biology fundamental problems is to discover genomic duplication events and their locations in the species tree. Such events can be reconstructed by clustering single gene duplications inferred by reconciling a set of gene trees with a species tree. Existing reconciliation based approaches vary in the two fundamental aspects: (a) the choice of evolutionary scenarios that model allowed locations of duplications in the species tree, and (b) the rules of clustering gene duplications from gene trees into a single multiple duplication event, i.e., episode clustering (EC) or minimum episodes (ME) methods. There are several models in the literature that specify how gene duplications from gene families can be interpreted as one duplication episode. However, in all duplication episode problems gene trees are rooted. This restriction limits the applicability, since unrooted gene family trees are frequently inferred by phylogenetic methods.In this dissertation, we propose a model of evolutionary scenarios that preserves the minimal number of gene duplications. We study the RME problem, that is, ME method of clustering when input gene trees are rooted. Our analysis concerns several models of allowed evolutionary scenarios with a focus on interval models in which every gene duplication has an interval consisting of allowed locations in the species tree and fulfills some additional requirements like monotonicity. We present mathematical foundations for general genomic duplication problems. Next, we propose the first linear time and space algorithm for RME jointly for any interval model and the algorithm for the most general model in which every evolutionary scenario is allowed. We also present a comparative study of different models of genomic duplication based on simulated and empirical datasets. We provide algorithms and tools that can be applied to solve RME problems efficiently for various models. Our comparative study helps to identify which model is the most reasonable choice in inferring genomic duplication events.This dissertation proposes the first solutions to the open problems of UEC (unrooted episode clustering) and UME (unrooted minimum episodes) in which every reconciliation with the minimal number of single gene duplications is allowed and under the assumption that input gene trees are unrooted. In particular, we show new theoretical properties of unrooted reconciliation for the duplication cost and apply them to design several exact and heuristic algorithms for solving the genomic duplication problems. Our comparative study shows that we can improve known results on genomic duplication inference from rooted trees. Moreover, our evaluation on empirical datasets confirms several genomic duplication events from the literature and demonstrates that the proposed algorithms can be successfully applied in practice.Jednym z fundamentalnych zagadnień w molekularnej biologii obliczeniowej jest wykrywanie zdarzeń duplikacji w genomie oraz określenie ich położenia w drzewie gatunków. Rekonstrukcja tych zdarzeń jest możliwa poprzez klastrowanie pojedynczych duplikacji genu, wyznaczonych przez uzgadnianie zbioru drzew genów ze zbiorem gatunków. Istniejące metody różnią się w dwóch zasadniczych kwestiach: (a) wyboru scenariuszy ewolucyjnych, które modelują dopuszczalne lokalizacje duplikacji w drzewie gatunków oraz (b) określenia zasad klastrowania duplikacji genów z drzew genów w jedno zdarzenie wielokrotnej duplikacji, metod jak np. episode clustering (EC) lub minimum episodes (ME). Analizując literaturę można wyróżnić kilka modeli opisujących jak duplikacje genów z drzew rodzin genów interpretować jako jedno zdarzenie, jednak wszystkie one dotyczą przypadku, gdy drzewa genów są ukorzenione. Warunek ten ogranicza możliwości zastosowań, gdyż to nieukorzenione drzewa genów są wynikiem popularnych metod filogenetycznych.W niniejszej rozprawie, proponujemy model scenariuszy ewolucyjnych, który zachowuje minimalną liczbę duplikacji genów. Badamy problem RME, czyli klastrowania metodą ME w przypadku, gdy wejściowe drzewa genów są ukorzenione. Przeanalizowaliśmy kilka modeli dopuszczalnych scenariuszy ewolucyjnych, ze szczególnym uwzględnieniem modeli interwałowych, w których każda duplikacja genu ma przypisany interwał dopuszczalnych lokalizacji w drzewie gatunków, oraz nakładających dodatkowe ograniczenia jak monotoniczność. Przedstawiamy matematyczne podstawy dla ogólnych problemów duplikacji genomowych. Następnie, dla problemu RME proponujemy pierwszy liniowy algorytm uniwersalny dla modeli interwałowych oraz algorytm dla najbardziej ogólnego modelu, w którym każdy scenariusz ewolucyjny jest dopuszczalny. Dodatkowo przedstawiamy studium porównawcze dla różnych modeli duplikacji genomowych, które bazuje na danych symulowanych i empirycznych. Dostarczamy algorytmów i narzędzi do efektywnego rozwiązywania problemów RME dla różnych modeli. Nasze studium porównawcze pozwala na zidentyfikowanie, który model stanowi najrozsądniejszy wybór przy wnioskowaniu zdarzeń duplikacji genomu.Niniejsza rozprawa przedstawia pierwsze rozwiązania dla otwartych problemów UEC (episode clustering) i UME (minimum episodes), w których każdy scenariusz implikujący minimalną liczbę pojedynczych duplikacji genu jest dopuszczalny oraz przyjmujemy założenie, że wejściowe drzewa genów są nieukorzenione. W szczególności prezentujemy nowe teoretyczne własności nieukorzenionego uzgadniania dla kosztu duplikacyjnego i wykorzystujemy je do zaprojektowania dokładnych i heurystycznych algorytmów rozwiązujących problemy duplikacji genomowych. Nasza ewaluacja eksperymentalna pokazuje, że potrafimy ulepszyć znane wyniki dla wnioskowania duplikacji genomowych z ukorzenionych drzew. Dodatkowo nasza analiza na empirycznych danych potwierdziła kilka zdarzeń duplikacji genomowych z literatury demonstrując, że proponowane algorytmy można z sukcesem wykorzystywać w praktyce

Unifying duplication episode clustering and gene-species mapping inference

Abstract We present a novel problem, called MetaEC, which aims to infer gene-species assignments in a collection of partially leaf-labeled gene trees labels by minimizing the size of duplication episode clustering (EC). This problem is particularly relevant in metagenomics, where incomplete data often poses a challenge in the accurate reconstruction of gene histories. To solve MetaEC, we propose a polynomial time dynamic programming (DP) formulation that verifies the existence of a set of duplication episodes from a predefined set of episode candidates. In addition, we design a method to infer distributions of gene-species mappings. We then demonstrate how to use DP to design an algorithm that solves MetaEC. Although the algorithm is exponential in the worst case, we introduce a heuristic modification of the algorithm that provides a solution with the knowledge that it is exact. To evaluate our method, we perform two computational experiments on simulated and empirical data containing whole genome duplication events, showing that our algorithm is able to accurately infer the corresponding events

TIRfinder: A Web Tool for Mining Class II Transposons Carrying Terminal Inverted Repeats

Transposable elements (TEs) can be found in virtually all known genomes; plant genomes are exceptionally rich in this kind of dispersed repetitive sequences. Current knowledge on TE proliferation dynamics places them among the main forces of molecular evolution. Therefore efficient tools to analyze TE distribution in genomes are needed that would allow for comparative genomics studies and for studying TE dynamics in a genome. This was our main motivation underpinning TIRfinder construction–-an efficient tool for mining class II TEs carrying terminal inverted repeats. TIRfinder takes as an input a genomic sequence and information on structural properties of a TE family, and identifies all TEs in the genome showing the desired structural characteristics. The efficiency and small memory requirements of our approach stem from the use of suffix trees to identify all DNA segments surrounded by user-specified terminal inverse repeats (TIR) and target site duplications (TSD) which together constitute a mask. On the other hand, the flexibility of the notion of the TIR/TSD mask makes it possible to use the tool for de novo detection. The main advantages of TIRfinder are its speed, accuracy and convenience of use for biologists. A web-based interface is freely available at http:/bioputer.mimuw.edu.pl/tirfindertool/

Cardiac magnetic resonance shows improved outcomes in patients with an ST-Segment elevation myocardial infarction and a high thrombus burden treated with adjuvant aspiration thrombectomy

There is a discrepancy between epicardial vessel patency and microcirculation perfusion in a third of patients treated with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Optimization with aspiration thrombectomy (AT) may reduce distal embolization and microvascular obstruction. The effect of AT in the treatment of STEMI is debatable. The purpose of this study was to use cardiac magnetic resonance (CMR) to determine whether AT influences microvascular obstruction (MVO), infarct size and left ventricular (LV) remodelling in STEMI patients. Sixty STEMI patients with a thrombus-occluded coronary artery were randomized in a 2:1 fashion to receive PCI proceeded by AT (AT + PCI group), or PCI only. MVO, myocardial infarct size and LV remodelling were assessed by CMR during the index hospitalization and 6 months thereafter. The majority of patients had a large thrombus burden (TIMI thrombus grade 5 in over 70% of patients). PCI and AT were effective in all cases. There were no periprocedural strokes. CMR showed that the addition of AT to standard PCI was associated with lesser MVO when indexed to the infarct size and larger infarct size reduction. There were less patients with left ventricle remodelling in the AT + PCI vs. the PCI only group. To conclude, in STEMI patients with a high thrombus burden, AT added to PCI is effective in reducing infarct size, MVO and LV remodelling

Quantitative analysis reveals crosstalk mechanisms of heat shock-induced attenuation of NF-κB signaling at the single cell level

<div><p>Elevated temperature induces the heat shock (HS) response, which modulates cell proliferation, apoptosis, the immune and inflammatory responses. However, specific mechanisms linking the HS response pathways to major cellular signaling systems are not fully understood. Here we used integrated computational and experimental approaches to quantitatively analyze the crosstalk mechanisms between the HS-response and a master regulator of inflammation, cell proliferation, and apoptosis the Nuclear Factor κB (NF-κB) system. We found that populations of human osteosarcoma cells, exposed to a clinically relevant 43°C HS had an attenuated NF-κB p65 response to Tumor Necrosis Factor α (TNFα) treatment. The degree of inhibition of the NF-κB response depended on the HS exposure time. Mathematical modeling of single cells indicated that individual crosstalk mechanisms differentially encode HS-mediated NF-κB responses while being consistent with the observed population-level responses. In particular “all-or-nothing” encoding mechanisms were involved in the HS-dependent regulation of the IKK activity and IκBα phosphorylation, while others involving transport were “analogue”. In order to discriminate between these mechanisms, we used live-cell imaging of nuclear translocations of the NF-κB p65 subunit. The single cell responses exhibited “all-or-nothing” encoding. While most cells did not respond to TNFα stimulation after a 60 min HS, 27% showed responses similar to those not receiving HS. We further demonstrated experimentally and theoretically that the predicted inhibition of IKK activity was consistent with the observed HS-dependent depletion of the IKKα and IKKβ subunits in whole cell lysates. However, a combination of “all-or-nothing” crosstalk mechanisms was required to completely recapitulate the single cell data. We postulate therefore that the heterogeneity of the single cell responses might be explained by the cell-intrinsic variability of HS-modulated IKK signaling. In summary, we show that high temperature modulates NF-κB responses in single cells in a complex and unintuitive manner, which needs to be considered in hyperthermia-based treatment strategies.</p></div

Mathematical modeling discriminates different single cell HS encoding mechanisms.

<p>(<b>A</b>) HS effect is modeled via a time-dependent attenuation function y(t). Each model simulation consists of three steps: (I) randomization of the attenuation coefficient <i>R</i> from the gamma distribution, (II) calculation of the attenuation function y(t) for the given <i>R</i>, (III) NF-κB model simulation. (<b>B</b>) List of considered cross-talk mechanisms. Roman numerals refer to mechanisms depicted in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006130#pcbi.1006130.g002" target="_blank">Fig 2</a>. Reverse effect indicates activation. (<b>C</b>) Schematic diagram of NF-κB model. Colored arrows indicate simulated cross-talk mechanism from B. (<b>D</b>) Simulation of hypothetical mechanisms involved in the NF-κB and HS pathway cross-talk. Simulations performed for 60 min HS exposure before TNFα stimulation. Shown are a sample of 50 time courses of simulated nuclear NF-κB levels (colored lines) and average nuclear NF-κB levels (black bold line), calculated from 1,000 single cell simulations for cells treated with TNFα. (<b>E</b>) Scatterplots of the maximum nuclear NF-κB against the attenuation coefficient <i>R</i> per simulated cell. Color scheme refers to “all-or-nothing” or “analogue” encoding, as well as mechanisms where a population-level fit was not obtained (no effect).</p

Temporal encoding of HS crosstalk.

<p>(<b>A</b>) Simulation of HS cross-talk assuming IKK depletion and inhibition of IKK activation (model b*+c from <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006130#pcbi.1006130.g007" target="_blank">Fig 7</a>). Shown are a sample of 50 time courses of simulated nuclear NF-κB levels (colored lines) and average nuclear NF-κB levels (black bold line), calculated from 1,000 single cell simulations for cells treated with TNFα after different HS exposure times. <b>(B)</b> Percentage (%) of responding (yellow) and non-responding (blue) cells from A. <b>(C)</b> Characteristics of NF-κB trajectories in responding cells from B. Left panel: the distribution of the maximum nuclear NF-κB. Right panel: time to first response. <b>(D)</b> Scatterplots of the maximum nuclear NF-κB level per cell against (I) attenuation coefficient <i>R</i>, (II) IKKn level before HS and (III) IKKn at time t₀ (after 60 min HS, before TNFα treatment). <b>(E)</b> Fitted IKKn levels after different HS exposure times (calculated from data in A).</p