Slipping motions of magnetic field lines are a distinct signature of three-dimensional magnetic reconnection, a fundamental process driving solar and stellar flares. While being a key prediction of numerical experiments, the rapid super-Alfvénic field line slippage driven by the 'slip-running' reconnection has remained elusive in previous observations. New frontiers into exploring transient flare phenomena were introduced by recently designed high cadence observing programs of the Interface Region Imaging Spectrograph (IRIS). By exploiting high temporal resolution imagery (~2 s) of IRIS, here we reveal slipping motions of flare kernels at speeds reaching thousands of kilometres per second. The fast kernel motions are direct evidence of slip-running reconnection in quasi-separatrix layers, regions where magnetic field strongly changes its connectivity. Our results provide observational proof of theoretical predictions unaddressed for nearly two decades and extend the range of magnetic field configurations where reconnection-related phenomena can occur.

• Klíčová slova
• Astrophysical magnetic fields, Astrophysical plasmas, Solar physics,
• Publikační typ
• časopisecké články MeSH

Bilirubin (BR) is a water-insoluble product of heme catabolism in mammals. Elevated blood concentrations of BR, especially in the neonatal period, are treated with blue-green light phototherapy. The major mechanism of BR elimination during phototherapy is photoisomerization, while a minor, less studied mechanism of degradation is oxidation. In this work, we studied the oxidation of the bilirubin model tetramethyl-dipyrrinone (Z-13) by singlet oxygen in methanol using UV-vis and ESI-MS spectroscopy, resulting in propentdyopents as the main oxidation products. We also identified two additional intermediates that were formed during the reaction (hydroperoxide 21a and imine 17). The structure of the hydroperoxide was confirmed by helium-tagging IR spectroscopy. Such reaction intermediates formed during the oxidation of BR or bilirubin models have not been described so far. We believe that this work can be used as a first step in studying the complex oxidation mechanism of BR during phototherapy.

• MeSH
• bilirubin chemie   MeSH
• fotochemické procesy MeSH
• metamizol chemie   MeSH
• molekulární struktura MeSH
• oxidace-redukce * MeSH
• singletový kyslík * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bilirubin MeSH
• metamizol MeSH
• singletový kyslík * MeSH

Asteroid discoveries are essential for planetary-defence efforts aiming to prevent impacts with Earth1, including the more frequent2 megaton explosions from decametre impactors3-6. Although large asteroids (≥100 kilometres) have remained in the main belt since their formation7, small asteroids are commonly transported to the near-Earth object (NEO) population8,9. However, owing to the lack of direct observational constraints, their size-frequency distribution (SFD)-which informs our understanding of the NEOs and the delivery of meteorite samples to Earth-varies substantially among models10-14. Here we report 138 detections of some of the smallest asteroids (≳10 metres) ever observed in the main belt, which were enabled by JWST's infrared capabilities covering the emission peaks of the asteroids15 and synthetic tracking techniques16-18. Despite small orbital arcs, we constrain the distances and phase angles of the objects using known asteroids as proxies, allowing us to derive sizes through radiometric techniques. Their SFD shows a break at about 100 metres (debiased cumulative slopes of q = -2.66 ± 0.60 and -0.97 ± 0.14 for diameters smaller and larger than roughly 100 metres, respectively), suggestive of a population driven by collisional cascade. These asteroids were sampled from several asteroid families-most probably Nysa, Polana and Massalia-according to the geometry of pointings considered here. Through further long-stare infrared observations, JWST is poised to serendipitously detect thousands of decametre-scale asteroids across the sky, examining individual asteroid families19 and the source regions of meteorites13,14 'in situ'.

• Publikační typ
• časopisecké články MeSH

The sacroiliac joint (SIJ) exhibits significant variation in auricular surface morphology. This variation influences the mechanics of the SIJ, a central node for transmitting mechanical energy from upper body to lower limbs and vice versa. The impact of the auricular surface morphology on stress and deformation in the SIJ remains poorly understood to date. Computed tomography scans obtained from 281 individuals were included to extract the geometry of the pelvic ring. Then, the auricular surface area, SIJ cartilage thickness, and total SIJ cartilage volume were identified. Based on these reconstructions, 281 finite element models were created to simulate SIJ mechanical loading. It was found that SIJ cartilage thickness only weakly depended on age or laterality, while being strongly sex sensitive. Auricular surface area and SIJ cartilage volume depended weakly and non-linearly on age, peaking around menopause in females, but without significant laterality effect. Larger SIJs, characterized by greater auricular area and cartilage volume, exhibited reduced stress and deformation under loading. These findings highlight the significant role of SIJ morphology in its biomechanical response, suggesting a potential link between morphological variations and the risk of SIJ dysfunction. Understanding this relationship could improve diagnosis and targeted treatment strategies for SIJ-related conditions.

• Klíčová slova
• finite element simulation, machine learning, sacroiliac joint anatomy,
• MeSH
• analýza metodou konečných prvků MeSH
• biomechanika fyziologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mechanický stres MeSH
• mladiství MeSH
• mladý dospělý MeSH
• počítačová rentgenová tomografie * MeSH
• sakroiliakální kloub * anatomie a histologie   fyziologie   diagnostické zobrazování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Mismatched nucleobase uracil is commonly repaired through the base excision repair initiated by DNA uracil glycosylases. The data presented in this study strongly indicate that the nuclear uracil-N-glycosylase activity and nuclear protein content in human cell lines is highest in the S phase of the cell cycle and that its distribution kinetics partially reflect the DNA replication activity in replication foci. In this respect, the data demonstrate structural changes of the replication focus related to the uracil-N-glycosylase distribution several dozens of minutes before end of its replication. The analysis also showed that very popular synchronisation protocols based on the double thymidine block can result in changes in the UNG2 content and uracil excision rate. In response, we propose a new method for the description of the changes of the content and the activity of different cell components during cell cycle without the necessity to use synchronisation protocols.

• MeSH
• buněčné jádro metabolismus   MeSH
• buněčný cyklus MeSH
• kinetika MeSH
• lidé MeSH
• oprava DNA MeSH
• replikace DNA * MeSH
• S fáze MeSH
• uracil-DNA-glykosidasa * metabolismus   MeSH
• uracil metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• uracil-DNA-glykosidasa * MeSH
• uracil MeSH

Electrical cardioversion presents one of the treatment options for atrial fibrillation (AF). However, the early recurrence rate is high, reaching ~40% three months after the procedure. Features based on vectorcardiographic signals were explored to find association with early recurrence of AF. Eighty-four patients with non-paroxysmal AF referred to electrical cardioversion were prospectively studied; early AF recurrence was present in 40 (47.6%). Patients underwent 24-h Holter ECG monitoring three months after the procedure to assess AF recurrence. Pre-procedural 12-lead ECGs (10 s, 1 kHz) were recorded and automatically analyzed. We explored associations of VCG-based features with early AF recurrence. Two features were strongly associated with AF recurrence: (1) a mean VCG (y-axis) signal slope in a window starting 145 ms before QRS center, lasting for 190 ms (AUC 0.778, p < 0.001), and (2) a mean VCG (z-axis) signal slope in a window starting 60 ms after QRS center, lasting for 465 ms (AUC 0.744, p < 0.001). These features showed higher association to the outcome than eighteen baseline clinical features. Our approach revealed features based on a slope of vectorcardiographic signals. This work also suggests that state of ventricles strongly affects the AF recurrence after electrical cardioversion.

• Klíčová slova
• Atrial fibrillation, Cardioversion, ECG, Signal processing, VCG,
• MeSH
• elektrická defibrilace * MeSH
• elektrokardiografie ambulantní MeSH
• fibrilace síní * terapie   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• recidiva * MeSH
• senioři MeSH
• vektorkardiografie * metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Purpose To develop a deep learning tool for the automatic segmentation of the spinal cord and intramedullary lesions in spinal cord injury (SCI) on T2-weighted MRI scans. Materials and Methods This retrospective study included MRI data acquired between July 2002 and February 2023. The data consisted of T2-weighted MRI scans acquired using different scanner manufacturers with various image resolutions (isotropic and anisotropic) and orientations (axial and sagittal). Patients had different lesion etiologies (traumatic, ischemic, and hemorrhagic) and lesion locations across the cervical, thoracic, and lumbar spine. A deep learning model, SCIseg (which is open source and accessible through the Spinal Cord Toolbox, version 6.2 and above), was trained in a three-phase process involving active learning for the automatic segmentation of intramedullary SCI lesions and the spinal cord. The segmentations from the proposed model were visually and quantitatively compared with those from three other open-source methods (PropSeg, DeepSeg, and contrast-agnostic, all part of the Spinal Cord Toolbox). The Wilcoxon signed rank test was used to compare quantitative MRI biomarkers of SCI (lesion volume, lesion length, and maximal axial damage ratio) derived from the manual reference standard lesion masks and biomarkers obtained automatically with SCIseg segmentations. Results The study included 191 patients with SCI (mean age, 48.1 years ± 17.9 [SD]; 142 [74%] male patients). SCIseg achieved a mean Dice score of 0.92 ± 0.07 and 0.61 ± 0.27 for spinal cord and SCI lesion segmentation, respectively. There was no evidence of a difference between lesion length (P = .42) and maximal axial damage ratio (P = .16) computed from manually annotated lesions and the lesion segmentations obtained using SCIseg. Conclusion SCIseg accurately segmented intramedullary lesions on a diverse dataset of T2-weighted MRI scans and automatically extracted clinically relevant lesion characteristics. Keywords: Spinal Cord, Trauma, Segmentation, MR Imaging, Supervised Learning, Convolutional Neural Network (CNN) Published under a CC BY 4.0 license.

• Klíčová slova
• Convolutional Neural Network (CNN), MR Imaging, Segmentation, Spinal Cord, Supervised Learning, Trauma,
• MeSH
• deep learning * MeSH
• dospělí MeSH
• interpretace obrazu počítačem metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• poranění míchy * diagnostické zobrazování   patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Connections between the mechanical properties of DNA and biological functions have been speculative due to the lack of methods to measure or predict DNA mechanics at scale. Recently, a proxy for DNA mechanics, cyclizability, was measured by loop-seq and enabled genome-scale investigation of DNA mechanics. Here, we use this dataset to build a computational model predicting bias-corrected intrinsic cyclizability, with near-perfect accuracy, solely based on DNA sequence. Further, the model predicts intrinsic bending direction in 3D space. Using this tool, we aimed to probe mechanical selection - that is, the evolutionary selection of DNA sequence based on its mechanical properties - in diverse circumstances. First, we found that the intrinsic bend direction of DNA sequences correlated with the observed bending in known protein-DNA complex structures, suggesting that many proteins co-evolved with their DNA partners to capture DNA in its intrinsically preferred bent conformation. We then applied our model to large-scale yeast population genetics data and showed that centromere DNA element II, whose consensus sequence is unknown, leaving its sequence-specific role unclear, is under mechanical selection to increase the stability of inner-kinetochore structure and to facilitate centromeric histone recruitment. Finally, in silico evolution under strong mechanical selection discovered hallucinated sequences with cyclizability values so extreme that they required experimental validation, yet, found in nature in the densely packed mitochondrial(mt) DNA of Namystynia karyoxenos, an ocean-dwelling protist with extreme mitochondrial gene fragmentation. The need to transmit an extraordinarily large amount of mtDNA, estimated to be > 600 Mb, in combination with the absence of mtDNA compaction proteins may have pushed mechanical selection to the extreme. Similarly extreme DNA mechanics are observed in bird microchromosomes, although the functional consequence is not yet clear. The discovery of eccentric DNA mechanics in unrelated unicellular and multicellular eukaryotes suggests that we can predict extreme natural biology which can arise through strong selection. Our methods offer a way to study the biological functions of DNA mechanics in any genome and to engineer DNA sequences with desired mechanical properties.

• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

BACKGROUND: Long terminal repeats (LTRs) represent important parts of LTR retrotransposons and retroviruses found in high copy numbers in a majority of eukaryotic genomes. LTRs contain regulatory sequences essential for the life cycle of the retrotransposon. Previous experimental and sequence studies have provided only limited information about LTR structure and composition, mostly from model systems. To enhance our understanding of these key sequence modules, we focused on the contrasts between LTRs of various retrotransposon families and other genomic regions. Furthermore, this approach can be utilized for the classification and prediction of LTRs. RESULTS: We used machine learning methods suitable for DNA sequence classification and applied them to a large dataset of plant LTR retrotransposon sequences. We trained three machine learning models using (i) traditional model ensembles (Gradient Boosting), (ii) hybrid convolutional/long and short memory network models, and (iii) a DNA pre-trained transformer-based model using k-mer sequence representation. All three approaches were successful in classifying and isolating LTRs in this data, as well as providing valuable insights into LTR sequence composition. The best classification (expressed as F1 score) achieved for LTR detection was 0.85 using the hybrid network model. The most accurate classification task was superfamily classification (F1=0.89) while the least accurate was family classification (F1=0.74). The trained models were subjected to explainability analysis. Positional analysis identified a mixture of interesting features, many of which had a preferred absolute position within the LTR and/or were biologically relevant, such as a centrally positioned TATA-box regulatory sequence, and TG..CA nucleotide patterns around both LTR edges. CONCLUSIONS: Our results show that the models used here recognized biologically relevant motifs, such as core promoter elements in the LTR detection task, and a development and stress-related subclass of transcription factor binding sites in the family classification task. Explainability analysis also highlighted the importance of 5'- and 3'- edges in LTR identity and revealed need to analyze more than just dinucleotides at these ends. Our work shows the applicability of machine learning models to regulatory sequence analysis and classification, and demonstrates the important role of the identified motifs in LTR detection.

• Klíčová slova
• CNN-LSTM, DNABERT, Deep learning, Eukaryote, Regulatory mechanisms, Repeat, SHAP score, Sequence analysis, TFBS, Transcription factor binding sites, Transposable elements,
• Publikační typ
• časopisecké články MeSH

Transcription factors (TFs) are key players in eukaryotic gene regulation, but the DNA binding specificity of many TFs remains unknown. Here, we assayed 284 mostly poorly characterized, putative human TFs using selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq), revealing 72 new DNA binding motifs. To investigate whether some of the 158 TFs for which we did not find motifs preferably bind epigenetically modified DNA (i.e. methylated CG dinucleotides), we developed methylation-sensitive SMiLE-seq (meSMiLE-seq). This microfluidic assay simultaneously probes the affinity of a protein to methylated and unmethylated DNA, augmenting the capabilities of the original method to infer methylation-aware binding sites. We assayed 114 TFs with meSMiLE-seq and identified DNA-binding models for 48 proteins, including the known methylation-sensitive binding modes for POU5F1 and RFX5. For 11 TFs, binding to methylated DNA was preferred or resulted in the discovery of alternative, methylation-dependent motifs (e.g. PRDM13), while aversion towards methylated sequences was found for 13 TFs (e.g. USF3). Finally, we uncovered a potential role for ZHX2 as a putative binder of Z-DNA, a left-handed helical DNA structure which is adopted more frequently upon CpG methylation. Altogether, our study significantly expands the human TF codebook by identifying DNA binding motifs for 98 TFs, while providing a versatile platform to quantitatively assay the impact of DNA modifications on TF binding.

• Publikační typ
• časopisecké články MeSH
• preprinty MeSH