Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational modeling reveals cell-cycle dependent kinetics of H4K20 methylation states during Xenopus embryogenesis

Histone modifications regulate chromatin architecture and thereby control gene expression. Rapid cell divisions and DNA replication however lead to a dilution of histone modifications and can thus affect chromatin mediated gene regulation So how does the cell-cycle shape the histone modification landscape, in particular during embryogenesis when a fast and precise control of cell-specific gene expression is required? We addressed this question in vivo by manipulating the cell-cycle during early Xenopus laevis embryogenesis. The global distribution of un-, mono- di- and tri-methylated histone H4K20 was measured by mass spectrometry in normal and cell-cycle arrested embryos over time. Using multi-start maximum likelihood optimization and quantitative model selection, we found that three specific methylation rate constants were required to explain the measured H4K20 methylation state kinetics. Interestingly, demethylation was found to be redundant in the cycling embryos but essential in the cell-cycle arrested embryos. Together, we present the first quantitative analysis of in vivo histone H4K20 methylation kinetics. Our computational model shows that demethylation is only essential for regulating H4K20 methylation kinetics in non-cycling cells. In rapidly dividing cells of early embryos, we predict that demethylation is dispensable, suggesting that cell-cycle mediated dilution of chromatin marks is an essential regulatory component for shaping the epigenetic landscape during early embryonic development.
Rationalizing PROTAC-mediated ternary complex formation using Rosetta

PROTACs are molecules that combine a target-binding warhead with an E3 ligase-recruiting moiety; by drawing the target protein into a ternary complex with the E3 ligase, PROTACs induce target protein degradation. While PROTACs hold exciting potential as chemical probes and as therapeutic agents, development of a PROTAC typically requires synthesis of numerous analogs to thoroughly explore variations on the chemical linker; without extensive trial and error, it is unclear how to link the two protein-recruiting moieties to promote formation of a productive ternary complex. Here, we describe a structure-based computational method for evaluating suitability of a given linker for ternary complex formation. Our method uses Rosetta to dock the protein components, then builds the PROTAC from its component fragments into each binding mode; complete models of the ternary complex are then refined. We apply this approach to retrospectively evaluate multiple PROTACs from the literature, spanning diverse target proteins. We find that modeling ternary complex formation is sufficient to explain both activity and selectivity reported for these PROTACs, implying that other cellular factors are not key determinants of activity in these cases. We further find that interpreting PROTAC activity is best approached using an ensemble of structures of the ternary complex rather than a single static conformation, and that members of a structurally-conserved protein family can be recruited by the same PROTAC through vastly different binding modes. To encourage adoption of these methods and promote further analyses, we disseminate both the computational methods and the models of ternary complexes. Significance Statement Recent years have brought a flood of interest in developing compounds that selectively degrade protein targets in cells, as exemplified by PROTACs. Fully realizing the promise of PROTACs to transform chemical biology by delivering degraders of diverse and undruggable protein targets has been impeded, however, by the fact that designing a suitable chemical linker between the functional moieties requires extensive trial and error. Here, we describe a structure-based computational method to predict PROTAC activity. We envision that this approach will allow design and optimization of PROTACs for efficient target degradation, selection of E3 ligases best suited for pairing with a given target protein, and understanding the basis by which PROTACs can exhibit different target selectivity than their component warheads.
Genome-wide Association Studies Reveal Important Candidate Genes for the Bacillus pumilus TUAT-1-Arabidopsis thaliana Interaction

The plant growth promoting bacterium (PGPB) Bacillus pumilus TUAT-1 is an indole acetic acid producer that can increase plant growth. Inoculation with this strain has been shown to confer greater plant tolerance to drought and saline conditions. Although the ability of TUAT-1 to enhance plant growth is well documented, little is known about what mechanisms underlie the plant response to this bacterium. Applying genome-wide association study (GWAS), we evaluated the interaction between TUAT-1 and Arabidopsis thaliana, screening 288 plant ecotypes for root architecture traits comparing non-inoculated and inoculated plants. Most of the ecotypes were significantly affected by TUAT-1 inoculation (66.7%) for at least one of the root traits measured. For example, some ecotypes responded positively increasing root growth while others showed reduced growth upon inoculation. A total of 96 ecotypes (33.3%) did not respond significantly to PGPB inoculation. These results are consistent with the widely reported strain-genotype specificity shown in many plant-microbe interactions. The GWAS analysis revealed significant SNPs associated to specific root traits leading to identification of several genes putatively involved in enabling the Bacillus pumilus TUAT-1 and A. thaliana association and contributing to plant growth promotion. Our results show that root architecture features are genetic separable traits associated with plant growth in association with TUAT-1. Our findings validate previous reported genes involved in Bacillus spp. -plant interaction, growth promotion and highlight potential genes involved in plant microbe interaction. We suggest that plant-bacterial interaction and the plant growth promotion are quantitative and multigenic traits. This knowledge expands our understanding of the functional mechanisms driving plant growth promotion by PGPB.
AMPK regulates cell shape of cardiomyocytes by modulating turnover of microtubules through CLIP-170

AMP-activated protein kinase (AMPK) is a multifunctional kinase that regulates microtubule (MT) dynamic instability through CLIP-170 phosphorylation; however, its physiological relevance in vivo remains to be elucidated. In this study, we identified an active form of AMPK localized at the intercalated discs in the heart, a specific cell-cell junction present between cardiomyocytes. A contractile inhibitor, MYK-461, prevented the localization of AMPK at the intercalated discs, and the effect was reversed by the removal of MYK-461, suggesting that the localization of AMPK is regulated by mechanical stress. Time-lapse imaging analysis revealed that the inhibition of CLIP-170 Ser-311 phosphorylation by AMPK leads to the accumulation of MTs at the intercalated discs. Interestingly, MYK-461 increased the individual cell area of cardiomyocytes in CLIP-170 phosphorylation-dependent manner. Moreover, heart-specific CLIP-170 S311A transgenic mice demonstrated elongation of cardiomyocytes along with accumulated MTs, leading to progressive decline in cardiac contraction. In conclusion, these findings suggest that AMPK regulates the cell shape and aspect ratio of cardiomyocytes by modulating the turnover of MTs through homeostatic phosphorylation of CLIP-170 at the intercalated discs.
Catalytic DNAzymes: derivations and functions

Background: Although catalytic RNA enzymes (CRzs) are naturally occurring in many organisms, their DNA counterparts (CDzs) were developed by in vitro selection/evolution from random sequence libraries. Objective: To provide a brief overview of how CDzs have been selected in vitro, and of their properties and functions, as well as their possible future utility. Methods: We concentrated on examples of ‘direct’ selection of CDzs. Many CDzs have been used in biological settings, for example downregulation of target mRNAs, while many more recent applications use CDzs in biosensor and nanotechnology settings. Conclusions: Although much work has concentrated on using CDzs for regulating gene expression, their potential as nucleic acid medicines has diminished substantially, supplanted by simple antisense oligonucleotides and, more recently, by small interfering RNAs (siRNAs). It seems unlikely that CDzs will have clinical utility. In contrast, they are likely to have significant potential in the sensor/nanotechnology arena.
Insights into the evolution of symbiosis gene copy number and distribution from a chromosome-scale Lotus japonicus Gifu genome sequence

Aim Lotus japonicus is a herbaceous perennial legume that has been used extensively as a genetically tractable model system for deciphering the molecular genetics of symbiotic nitrogen fixation. Our aim is to improve the L. japonicus reference genome sequence, which has so far been based on Sanger and Illumina sequencing reads from the L. japonicus accession MG-20 and contained a large fraction of unanchored contigs. Methods and Results Here, we use long PacBio reads from L. japonicus Gifu combined with Hi-C data and new high-density genetic maps to generate a high-quality chromosome-scale reference genome assembly for L. japonicus. The assembly comprises 554 megabases of which 549 were assigned to six pseudomolecules that appear complete with telomeric repeats at their extremes and large centromeric regions with low gene density. Conclusion and Perspectives The new L. japonicus Gifu reference genome and associated expression data represent valuable resources for legume functional and comparative genomics. Here, we provide a first example by showing that the symbiotic islands recently described in Medicago truncatula do not appear to be conserved in L. japonicus.
Sperm Motility of Northern Pike and Chain Pickerel at Various pH Values

Abstract The activity of sperm from northern pike Esox lucius and chain pickerel Esox niger was observed at pH 3.9, 4.5, 5.4, 6.0, 6.4, 6.9, 7.4, and 7.9. The sperm of the northern pike remained motile for shorter periods of time than that of the chain pickerel (P = 0.01). Northern pike sperm was not observed swimming actively at pH values less than pH 5.4 and showed a strong trend toward increased time of activity with increasing pH. For this species, minimum motility occurred at pH 5.4 (28 seconds) and maximum motility was found at pH 7.9 (67 seconds). In contrast, chain pickerel sperm was acid-tolerant, swimming actively for periods of over 90 seconds at pH 3.9 and 4.5. Maximum sperm motility for this species was at pH 6.9 (137 seconds). Motility time for chain pickerel sperm was reduced at the two most basic levels tested: 109 seconds at pH 7.4, and 81 seconds at pH 7.9. Substantial variation in sperm motility time occurred between the two chain pickerel males tested, but not between the two northern .
Model of Process Management System in Enterprises of the Hard Coal Mining Industry

Abstract The primary objective of this paper is to present a model of a process management system developed to support the restructuring of Polish enterprises of the hard coal mining industry. The development of this model required research in three stages using several research methods. The stage I of the research was oriented towards the recognition of the existing state of knowledge in the scope of previously developed models of process management in enterprises. At this stage, a method of reviewing the literature, the analysis and synthesis of the results of considerations, was used. The stage II was oriented towards presenting of the current state of knowledge in the field of process management to the managerial staff of mines in order to identify their needs, capabilities and preferences. The research were attended by 24 managers from PGG SA and JSW SA. At this stage, the method of targeted free-form interview and discussions, was used. The stage III of the research was oriented towards the development of a process management system model in enterprises operating in the hard coal mining industry, based on the scientific achievements to date in the field of process management and consensus on the needs, preferences and capabilities of mine managerial staff with regard to its specific elements. At this stage, the method of analysis and synthesis was used. The results of the research presented in this publication are primarily addressed to the managerial staff of polish hard mines, as they provide a synthesized response to the problem of the lack of consistent process management guidelines that could set a standard within a mining enterprise. The model presented in the publication is of a general nature, although it may provide a basis for the application of process management for mines.
Integration of Time and Spatially Resolved In-Situ Temperature and Pressure Measurements With Soft Ionisation Mass Spectrometry Inside Burning Superslim and King-Size Cigarettes

Summary Background Combustion as well as pyrolysis of tobacco greatly affect the type and levels of toxicants in cigarette smoke. We previously developed an approach to combine simultaneous temperature and pressure measurements with fast in-situ microprobe chemical sampling inside a burning cigarette, producing a series of temperature and gas-flow velocity maps that characterize this dynamic system in response to externally applied air flow. Aim Two cigarette types differing only in diameter were puffed under ISO 3308 and Health Canada Intense (HCI) regimes to further understand the dynamic interaction of air flow and cigarette design parameters on tobacco combustion and pyrolysis by applying the thermophysical and thermo-chemical mapping approach. Methods Three types of sampling probes were inserted, which are thermocouple arrays for gas-phase temperature, quartz tubes for pressure measurement, and a heated sampling microprobe coupled to a single-photon soft ionisation mass spectrometer for chemical analysis. Two kinds of similarly constructed cigarettes with the same blend were analysed: superslim (17 mm circumference) and king-size (24 mm circumference). Synchronization among the sampled signals was achieved by mapping two probes (e.g., temperature/chemistry or temperature/pressure) at a time. The physical and chemical events were visualised and compared between the cigarettes and puffing regimes. Results A series of temperature, pressure, and chemical maps were obtained for the superslim and king-size cigarettes under ISO and HCI conditions. The pressure in the burning cigarette was higher in the superslim cigarette, and the temperature distribution differed between the two cigarette formats. As expected, temperatures and pressures were higher under HCI puffing than under ISO puffing for both cigarette formats. Thermochemical maps for e.g., benzene and nitric oxide formation were qualitatively similar between the superslim and king-size cigarettes. For other substances the distribution was markedly different. Conclusion The application of multi-probe in-situ chemical sampling is suitable to analyse highly dynamic combustion and pyrolysis processes occurring inside the two types of cigarettes. Ultimately, a direct comparison of cigarette circumferences on the complex combustion processes and formation of smoke constituents was achieved. [Beitr. Tabakforsch. Int. 29 (2020) 44–54]
Estimating the distribution of a stochastic sum of IID random variables

Abstract Suggested is a non-parametric method and algorithm for estimating the probability distribution of a stochastic sum of independent identically distributed continuous random variables, based on combining and numerically inverting the associated empirical characteristic function (CF) derived from the observed data. This is motivated by classical problems in financial risk management, actuarial science, and hydrological modelling. This approach can be naturally generalized to more complex semi-parametric modelling and estimating approaches, e.g., by incorporating the generalized Pareto distribution fit for modelling heavy tails of the considered continuous random variables, or by considering the weighted mixture of the parametric CFs (used to incorporate the expert knowledge) and the empirical CFs (used to incorporate the knowledge based on the observed or historical data). The suggested numerical approach is based on combination of the Gil-Pelaez inversion formulae for deriving the probability distribution (PDF and CDF) from the associated CF and the trapezoidal quadrature rule used for the required numerical integration. The presented non-parametric estimation method is related to the bootstrap estimation approach, and thus, it shares similar properties. Applicability of the proposed estimation procedure is illustrated by estimating the aggregate loss distribution from the well-known Danish fire losses data.
Soil and Sand Contamination with Canine Intestinal Parasite Eggs as a Risk Factor for Human Health in Public Parks in Niš (Serbia)

Summary Regarding geographical distribution and clinical relevance, the most common canine geohelminths are Toxocara canis, ancylostomatids, and Trichuris vulpis. Canine intestinal parasites from the soil and sand present an important potential serious human health hazard, especially for the children preschool and school – age. This paper aimed to establish the degree of contamination of soil and sand with zoonotic parasites from the canine feces and the degree of risk they could pose for human health in public places and playgrounds in the city of Niš. Our parasitological study involved 200 soil samples and 50 sand samples from the public parks in the city of Niš in southeastern Serbia (43°19′15″N, 21°53′45″ E). From several locations, about 100 g of soil and sand was collected based on the bioclimatic indices. Parasitological diagnosis was performed using conventional qualitative and quantitative coprological methods, abiding by the recommendations about the diagnosis of parasitic diseases. In 38 – 46 % of soil samples and 40 % of sand samples seven species of endoparasites were diagnosed. In the samples of soil, a medium and high degree of contamination with the ascarid T. canis (14 – 22 %) was detected, as well as a low and medium degree of contamination with ancylostomatids (4 – 12 %), and in the samples of sand, a variable degree of contamination with the helminths T. canis (26 %) and A. alata (16 %) was found. A statistically significant difference was found in the contamination with A. alata eggs between the samples of sand and samples of soil. The studied public surfaces represent the reservoir of zoonotic parasites, which is a public health problem requiring a synergistic action of several factors to be successfully resolved, i.e. the implementation of prevention, surveillance, and control measures.
Life and Death of Coral Reefs

Introduction. Reefs and reef limestones in earth history. Reefs as dynamic systems. Bioerosion and coral-reef growth: a dynamic balance. Interactions between corals and their symbiotic algae. Diseases of coral-reef organisims. Organic production and decomposition. Reproduction and recruitment in corals: critical links in the persistence of reefs. Invertebrate predators and grazers. Effects of reef fishes on coral and algae. Indirect interactions on the coral reefs. Geographic differences in ecological processes on coral reefs. Ecosystem Interactions in the tropical coastal seascape. Diversity and distribution of reef organisms. Disturbances to reefs in recent times. Traditional coral-reefs fisheries management. Resource use: conflicts and management solutions. Implications for resource management. References. Index.
Airborne Oblique Imaging: Towards the Hybrid Era

Abstract If the use of oblique aerial camera systems is steadily growing for 3D capture of urban areas, their combination with a LiDAR unit seems to have all the potential to lead the airborne mapping sector a step forward. To fully exploit the complementary sensor behaviour, a new perspective should be adopted that looks beyond the traditional data processing chains and extends them towards an hybrid data processing concept. Assisted tie point matching, integrated sensor orientation and augmented 3D reconstruction are the keystones of a rigorous hybrid workflow for hybrid sensors. They should all rely on a deep understanding of the different properties of active and passive 3D imaging, and of the uncertainty components in their measurements. The paper will focus on the most recent answers to these issues, that open new opportunities for boosting the quality of the geospatial products w.r. t completeness, geometric quality, object detection and processing efficiency
Using LiDAR Point Clouds in Determination of the Scots Pine Stands Spatial Structure Meaning in the Conservation of Lichen Communities in “Bory Tucholskie” National Park

Abstract The aim of the research carried out in 2018 and financed by the Forest Fund was the analysis of biometric features and parameters of pine stands in the area of the “Bory Tucholskie” National Park (PNBT), where a program of active protection of lichen was initiated in 2017. Environmental analyses were conducted in relation to selected biometric features of trees and stands using laser scanning (LiDAR), including ULS (Unmanned Laser Scanning; RIEGL VUX-1) and TLS (Terrestrial Laser Scanning; FARO FOCUS 3D; X130). Thanks to the application of LiDAR technology, the structure of pine stands was precisely determined by means of a series of descriptive statistics characterizing the 3D spatial structure of vegetation. Using the Trees Crown Model (CHM), the analysis of the volume of tree crowns and the volume of space under canopy was performed. For the analysed sub-compartments, GIS solar analyses were carried out for the solar energy reaching the canopy and the ground level due to active protection of lichen. Multispectral photos were obtained using a specialized RedEdge-M camera (MicaSense) mounted on the UAV multi rotor platform Typhoon H520 (Yuneec). Flights with a thermal camera were also performed in order to detect places on the ground with high temperature. Plant indices: NDVI, NDRE, GNDVI and GRVI were also calculated for sub-compartments. The data obtained in 2017 and 2018 were the basis for spatial and temporal analyses of 4-D changes in stands which were related to the removal of some trees and organic layer (litter, moss layer).
A neural network assisted Metropolis adjusted Langevin algorithm

Abstract In this paper, we derive a Markov chain Monte Carlo (MCMC) algorithm supported by a neural network. In particular, we use the neural network to substitute derivative calculations made during a Metropolis adjusted Langevin algorithm (MALA) step with inexpensive neural network evaluations. Using a complex, high-dimensional blood coagulation model and a set of measurements, we define a likelihood function on which we evaluate the new MCMC algorithm. The blood coagulation model is a dynamic model, where derivative calculations are expensive and hence limit the efficiency of derivative-based MCMC algorithms. The MALA adaptation greatly reduces the time per iteration, while only slightly affecting the sample quality. We also test the new algorithm on a 2-dimensional example with a non-convex shape, a case where the MALA algorithm has a clear advantage over other state of the art MCMC algorithms. To assess the impact of the new algorithm, we compare the results to previously generated results of the MALA and the random walk Metropolis Hastings (RWMH).