Abstract
Advances in sequencing technologies have empowered epitranscriptomic profiling at the single-base resolution. Putative RNA modification sites identified from a single high-throughput ...experiment may contain one type of modification deposited by different writers or different types of modifications, along with false positive results because of the challenge of distinguishing signals from noise. However, current tools are insufficient for subtyping, visualization, and denoising these signals. Here, we present iMVP, which is an interactive framework for epitranscriptomic analysis with a nonlinear dimension reduction technique and density-based partition. As exemplified by the analysis of mRNA m
5
C and ModTect variant data, we show that iMVP allows the identification of previously unknown RNA modification motifs and writers and the discovery of false positives that are undetectable by traditional methods. Using putative m
6
A/m
6
Am sites called from 8 profiling approaches, we illustrate that iMVP enables comprehensive comparison of different approaches and advances our understanding of the difference and pattern of true positives and artifacts in these methods. Finally, we demonstrate the ability of iMVP to analyze an extremely large human A-to-I editing dataset that was previously unmanageable. Our work provides a general framework for the visualization and interpretation of epitranscriptomic data.
Abstract
m
5
C is one of the longest-known RNA modifications, however, its developmental dynamics, functions, and evolution in mRNAs remain largely unknown. Here, we generate quantitative mRNA m
5
C ...maps at different stages of development in 6 vertebrate and invertebrate species and find convergent and unexpected massive methylation of maternal mRNAs mediated by NSUN2 and NSUN6. Using
Drosophila
as a model, we reveal that embryos lacking maternal mRNA m
5
C undergo cell cycle delays and fail to timely initiate maternal-to-zygotic transition, implying the functional importance of maternal mRNA m
5
C. From invertebrates to the lineage leading to humans, two waves of m
5
C regulatory innovations are observed: higher animals gain cis-directed NSUN2-mediated m
5
C sites at the 5' end of the mRNAs, accompanied by the emergence of more structured 5'UTR regions; humans gain thousands of trans-directed NSUN6-mediated m
5
C sites enriched in genes regulating the mitotic cell cycle. Collectively, our studies highlight the existence and regulatory innovations of a mechanism of early embryonic development and provide key resources for elucidating the role of mRNA m
5
C in biology and disease.
Abstract
mRNA m5C, which has recently been implicated in the regulation of mRNA mobility, metabolism and translation, plays important regulatory roles in various biological events. Two types of m5C ...sites are found in mRNAs. Type I m5C sites, which contain a downstream G-rich triplet motif and are computationally predicted to be located at the 5′ end of putative hairpin structures, are methylated by NSUN2. Type II m5C sites contain a downstream UCCA motif and are computationally predicted to be located in the loops of putative hairpin structures. However, their biogenesis remains unknown. Here we identified NSUN6, a methyltransferase that is known to methylate C72 of tRNAThr and tRNACys, as an mRNA methyltransferase that targets Type II m5C sites. Combining the RNA secondary structure prediction, miCLIP, and results from a high-throughput mutagenesis analysis, we determined the RNA sequence and structural features governing the specificity of NSUN6-mediated mRNA methylation. Integrating these features into an NSUN6-RNA structural model, we identified an NSUN6 variant that largely loses tRNA methylation but retains mRNA methylation ability. Finally, we revealed a weak negative correlation between m5C methylation and translation efficiency. Our findings uncover that mRNA m5C is tightly controlled by an elaborate two-enzyme system, and the protein-RNA structure analysis strategy established may be applied to other RNA modification writers to distinguish the functions of different RNA substrates of a writer protein.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
m
C is one of the longest-known RNA modifications, however, its developmental dynamics, functions, and evolution in mRNAs remain largely unknown. Here, we generate quantitative mRNA m
C maps at ...different stages of development in 6 vertebrate and invertebrate species and find convergent and unexpected massive methylation of maternal mRNAs mediated by NSUN2 and NSUN6. Using Drosophila as a model, we reveal that embryos lacking maternal mRNA m
C undergo cell cycle delays and fail to timely initiate maternal-to-zygotic transition, implying the functional importance of maternal mRNA m
C. From invertebrates to the lineage leading to humans, two waves of m
C regulatory innovations are observed: higher animals gain cis-directed NSUN2-mediated m
C sites at the 5' end of the mRNAs, accompanied by the emergence of more structured 5'UTR regions; humans gain thousands of trans-directed NSUN6-mediated m
C sites enriched in genes regulating the mitotic cell cycle. Collectively, our studies highlight the existence and regulatory innovations of a mechanism of early embryonic development and provide key resources for elucidating the role of mRNA m
C in biology and disease.
In order to study the precursor information of infrared radiation temperature of coal containing macro-cracks during load bearing damage, infrared monitoring tests of coal instability damage under ...different crack inclination angles are designed. Based on the critical slowing down theory, the variance and autocorrelation coefficients of the infrared radiation temperature series are calculated to reflect the damage precursors and provide a theoretical basis for early warning of coal and rock dynamic hazards. The results show that the infrared radiation sequences of pre-cracked coals have a critical slowing down effect. The autocorrelation coefficient and the variance of MIRT curve can be more accurate to find the precursor time of instability. In the critical slowing down analysis, the variance is more stable, and the lag step has a great influence on the autocorrelation coefficient. The infrared precursory information of the coal is mostly about 80% to 85% of the peak stress or instability time, and the horizontal fracture will make the failure precursory appear in advance.
In inertial confinement fusion, quantitative and high-spatial resolution (Formula: see textm) measurements of the X-rays self-emitted by the hotspot are critical for studying the physical processes ...of the implosion stagnation stage. Herein, the 8 ± 0.39-keV monochromatic X-ray distribution from the entire hotspot is quantitatively observed in 5-Formula: see textm spatial resolution using a Kirkpatrick-Baez microscope, with impacts from the responses of the diagnosis system removed, for the first time, in implosion experiments at the 100 kJ laser facility in China. Two-dimensional calculations along with 2.5% P2 drive asymmetry and 0.3 ablator self-emission are congruent with the experimental results, especially for the photon number distribution, hotspot profile, and neutron yield. Theoretical calculations enabled a better understanding of the experimental results. Furthermore, the origins of the 17.81% contour profile of the deuterium-deuterium hotspot and the accurate Gaussian source approximation of the core emission area in the implosion capsule are clarified in detail. This work is significant for quantitatively exploring the physical conditions of the hotspot and updating the theoretical model of capsule implosion.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
At present, research on coal mine emergency rescue path optimization is mostly in the stage of computer simulation calculation. In order to further promote its application in the actual environment ...of complex roadway, a cross-platform mine emergency rescue path optimization scheme was proposed.Influencing factors of roadway passage are abstracted as impact factors for easy calculation, and actual length of the roadway and passage difficulty are combined to calculate equivalent value of the roadway; Dijkstra algorithm is adopted to solve mine emergency rescue path using the equivalent value as the path length; the emergency search path optimization algorithm can runs on platforms such as computers and mobile terminals taking advantage of the cross-platform nature of Unity engine. Practical application results show that the scheme can bypass road sections that are impassable due to accidents, and provide accurate and effective underground disaster avoidance paths, thus providing technical support for the field
Soft coal is characterized by low strength and weak bonds, which play a key role in the occurrence and development of dynamic disasters. A more thorough understanding of the failure mechanics and ...infrared radiation characteristics of soft coal at various moisture contents is needed. In this study, infrared radiation experiments were conducted for soft coal at various moisture contents. The results indicate that moisture content affects compressive strength and elastic modulus of soft coal with compressive strength and elastic modulus being highest at moderate. Moisture has a substantial influence on the infrared radiation of compressed coal samples. Soft coals with high moisture contents show a smaller fluctuation of the average infrared radiation temperature curve and a stronger direct relationship of temperature and stress in the linear elastic stage. The coal samples with various moisture contents show a warming trend during loading. The increased amplitude of infrared radiation temperature per unit stress shows a linear relationship with moisture content. A large number of high temperature red spots appear along the diagonal line of coal samples with 0% moisture content before fracture, while changes in the infrared thermal image of the coal sample with 4% moisture content were negligible during loading.
Aiming at the problem of insufficient accuracy caused by the insufficient mining of spatiotemporal features in the process of unsafe behavior and danger identification of construction personnel, the ...traditional two-stream convolution model is improved, and a two-stream convolution dangerous behavior recognition model based on Faster R-CNN-LSTM is proposed. In this model, the Faster R-CNN network is connected in parallel with the LSTM network. The Faster R-CNN network is used as the spatial flow, and the human spatial motion posture is divided into static and dynamic features to extract the anchor point features, respectively. The fusion of the two is used as the output of the spatial flow. An improved sliding long-term and short-term memory network is used in the time flow to increase the extraction ability of the time series features of the construction personnel. Finally, the two branches are fused in time and space to classify and identify whether the construction personnel wear safety helmets. The results show that the MAP of the improved Faster R-CNN-LSTM network framework is increased by 15%. The original CNN-LSTM network framework detected four targets, but there was one misdetection, with an accuracy of 91.48%. The improved frame detection accuracy reaches 99.99%, and there is no error detection. The proposed method is superior to the pre-improvement and other methods that can effectively identify the unsafe behavior of construction workers on construction sites and also has a good distinction effect on fuzzy actions.
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