We provide a high-level survey of multiscale molecular visualization techniques, with a focus on application-domain questions, challenges, and tasks. We provide a general introduction to molecular visualization basics and describe a number of domain-specific tasks that drive this work. These tasks, in turn, serve as the general structure of the following survey. First, we discuss methods that support the visual analysis of molecular dynamics simulations. We discuss, in particular, visual abstraction and temporal aggregation. In the second part, we survey multiscale approaches that support the design, analysis, and manipulation of DNA nanostructures and related concepts for abstraction, scale transition, scale-dependent modeling, and navigation of the resulting abstraction spaces. In the third part of the survey, we showcase approaches that support interactive exploration within large structural biology assemblies up to the size of bacterial cells. We describe fundamental rendering techniques as well as approaches for element instantiation, visibility management, visual guidance, camera control, and support of depth perception. We close the survey with a brief listing of important tools that implement many of the discussed approaches and a conclusion that provides some research challenges in the field.

• MeSH
• Bacteria MeSH
• DNA ultrastruktura   MeSH
• lidé MeSH
• molekulární modely MeSH
• nanostruktury * MeSH
• proteiny chemie   MeSH
• simulace molekulární dynamiky * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The brain's complex organization spans from molecular-level processes within neurons to large-scale networks, making it essential to understand this multiscale structure to uncover brain functions and address neurological disorders. Multiscale brain modeling has emerged as a transformative approach, integrating computational models, advanced imaging, and big data to bridge these levels of organization. This review explores the challenges and opportunities in linking microscopic phenomena to macroscopic brain functions, emphasizing the methodologies driving progress in the field. It also highlights the clinical potential of multiscale models, including their role in advancing artificial intelligence (AI) applications and improving healthcare technologies. By examining current research and proposing future directions for interdisciplinary collaboration, this work demonstrates how multiscale brain modeling can revolutionize both scientific understanding and clinical practice.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Clusters of a solute and a few solvent molecules obtained from molecular dynamics (MD) are a powerful tool to study solvation effects by advanced quantum chemical (QC) methods. For spectroscopic properties strongly dependent on the solvation, however, a large number of clusters are needed for a good convergence. In this work, a parallel variable selection (PVS) method is proposed that in some cases efficiently reduces the number of clusters needed for the averaging. The mass, charge, or atomic density MD distributions are used as a secondary variable to preselect the most probable cluster geometries used for averaging of solute spectral properties. When applied to nuclear magnetic resonance chemical shift of a model alcohol, the method allowed one to significantly reduce the total computational time, by a factor of 10. Even larger savings were achieved for the modeling of Raman and Raman optical activity spectra of (S)-lactamide molecule dissolved in water. The results thus suggest that the PVS method can be generally used for simulations of spectroscopic properties of solvated molecules and makes multiscale MD/QC computations more affordable.

• MeSH
• alkoholy chemie   MeSH
• kvantová teorie MeSH
• magnetická rezonanční spektroskopie MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• Ramanova spektroskopie MeSH
• simulace molekulární dynamiky * MeSH
• Publikační typ
• časopisecké články MeSH

Phosphate···π, also called anion···π, contacts occur between nucleobases and anionic phosphate oxygens (OP2) in r(GNRA) and r(UNNN) U-turn motifs (N = A,G,C,U; R = A,G). These contacts were investigated using state-of-the-art quantum-chemical methods (QM) to characterize their physicochemical properties and to serve as a reference to evaluate AMBER force field (AFF) performance. We found that phosphate···π interaction energies calculated with the AFF for dimethyl phosphate···nucleobase model systems are less stabilizing in comparison with double-hybrid DFT and that minimum contact distances are larger for all nucleobases. These distance stretches are also observed in large-scale AFF vs QM/MM computations and classical molecular dynamics (MD) simulations on several r(gcGNRAgc) tetraloop hairpins when compared to experimental data extracted from X-ray/cryo-EM structures (res. ≤ 2.5 Å) using the WebFR3D bioinformatic tool. MD simulations further revealed shifted OP2/nucleobase positions. We propose that discrepancies between the QM and AFF result from a combination of missing polarization in the AFF combined with too large AFF Lennard-Jones (LJ) radii of nucleobase carbon atoms in addition to an exaggerated short-range repulsion of the r-12 LJ repulsive term. We compared these results with earlier data gathered on lone pair···π contacts in CpG Z-steps occurring in r(UNCG) tetraloops. In both instances, charge transfer calculations do not support any significant n → π* donation effects. We also investigated thiophosphate···π contacts that showed reduced stabilizing interaction energies when compared to phosphate···π contacts. Thus, we challenge suggestions that the experimentally observed enhanced thermodynamic stability of phosphorothioated r(GNRA) tetraloops can be explained by larger London dispersion.

• MeSH
• fosfáty MeSH
• RNA * chemie   MeSH
• simulace molekulární dynamiky * MeSH
• termodynamika MeSH
• výpočetní biologie MeSH
• Publikační typ
• časopisecké články MeSH

The pyrimidine-pyrimidone (6-4) photoproduct (64-PP) is an important photoinduced DNA lesion constituting a mutational signature for melanoma. The structural impact of 64-PP on DNA complexed with histones affects the lesion mutagenicity and repair but remains poorly understood. Here we investigate the conformational dynamics of DNA-containing 64-PP within the nucleosome core particle by atomic-resolution molecular dynamics simulations and multiscale data analysis. We demonstrate that the histone core exerts important mechanical restraints that largely decrease global DNA structural fluctuations. However, the local DNA flexibility at the damaged site is enhanced due to imperfect structural adaptation to restraints imposed by the histone core. If 64-PP faces the histone core and is therefore not directly accessible by the repair protein, the complementary strand facing the solvent is deformed and exhibits higher flexibility than the corresponding strand in a naked, undamaged DNA. This may serve as an initial recognition signal for repair. Our simulations also pinpoint the structural role of proximal residues from the truncated histone tails.

• MeSH
• DNA chemie   MeSH
• histony chemie   MeSH
• konformace nukleové kyseliny MeSH
• pyrimidinové dimery chemie   MeSH
• simulace molekulární dynamiky * MeSH
• ultrafialové záření MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH

Although entropy-based measurements of gait dynamics are becoming widely used tools for fall risk assessment, their relationship to fall occurrence is still unclear. The aim of this study was hence to compare fallers and non-fallers in terms of gait dynamics assessed by the multiscale and Shannon entropy. This study included 139 participants, aged 60-80 years, divided into two groups according to fall occurrence during a 6-month prospective observation (38 fallers, 101 non-fallers). The methodology involved the use of the Tinetti balance assessment tool (TBAT) and 5min of overground walking with 3D accelerometers located near the L5 vertebra and shanks. We analyzed 150 strides for gait complexity, an index of complexity (CI), computed from multiscale entropy (MSE) and Shannon entropy (ShE) derived from the recurrence quantification analysis. We found no significant differences between groups in MSE and CI. The TBAT total score was significantly higher in non-fallers (P=0.033), however, both groups showed low risk of falls. ShE in the anterior-posterior direction from trunk and in the medial-lateral direction from the shanks were both significantly higher in fallers (P=0.020; P=0.024). ShE was negatively correlated with CI, the shank ShE in the vertical direction was positively correlated with TBAT. Taken together, our findings suggest that MSE is not able to distinguish between highly functional groups, whereas Shannon entropy seems to be sufficient in fall risk prediction.

• MeSH
• chůze (způsob) fyziologie   MeSH
• entropie * MeSH
• hodnocení rizik metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• posturální rovnováha fyziologie   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• úrazy pádem prevence a kontrola   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Although they form a unitary phenomenon, the relationship between extracranial M/EEG and transmembrane ion flows is understood only as a general principle rather than as a well-articulated and quantified causal chain. METHOD: We present an integrated multiscale model, consisting of a neural simulation of thalamus and cortex during stage N2 sleep and a biophysical model projecting cortical current densities to M/EEG fields. Sleep spindles were generated through the interactions of local and distant network connections and intrinsic currents within thalamocortical circuits. 32,652 cortical neurons were mapped onto the cortical surface reconstructed from subjects' MRI, interconnected based on geodesic distances, and scaled-up to current dipole densities based on laminar recordings in humans. MRIs were used to generate a quasi-static electromagnetic model enabling simulated cortical activity to be projected to the M/EEG sensors. RESULTS: The simulated M/EEG spindles were similar in amplitude and topography to empirical examples in the same subjects. Simulated spindles with more core-dominant activity were more MEG weighted. COMPARISON WITH EXISTING METHODS: Previous models lacked either spindle-generating thalamic neural dynamics or whole head biophysical modeling; the framework presented here is the first to simultaneously capture these disparate scales. CONCLUSIONS: This multiscale model provides a platform for the principled quantitative integration of existing information relevant to the generation of sleep spindles, and allows the implications of future findings to be explored. It provides a proof of principle for a methodological framework allowing large-scale integrative brain oscillations to be understood in terms of their underlying channels and synapses.

• MeSH
• biologické modely * MeSH
• dospělí MeSH
• elektroencefalografie * MeSH
• iontové kanály MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• magnetoencefalografie * MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozková kůra * MeSH
• nervová síť MeSH
• počítačová simulace MeSH
• stadia spánku * MeSH
• thalamus * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Error detection in motor behavior is a fundamental cognitive function heavily relying on local cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a multiscale picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies.

• MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• elektrokortikografie MeSH
• gama rytmus EEG fyziologie   MeSH
• lidé MeSH
• mapování mozku metody   MeSH
• mladý dospělý MeSH
• mozek fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

RATIONALE: Cardiac ECM (extracellular matrix) comprises a dynamic molecular network providing structural support to heart tissue function. Understanding the impact of ECM remodeling on cardiac cells during heart failure (HF) is essential to prevent adverse ventricular remodeling and restore organ functionality in affected patients. OBJECTIVES: We aimed to (1) identify consistent modifications to cardiac ECM structure and mechanics that contribute to HF and (2) determine the underlying molecular mechanisms. METHODS AND RESULTS: We first performed decellularization of human and murine ECM (decellularized ECM) and then analyzed the pathological changes occurring in decellularized ECM during HF by atomic force microscopy, 2-photon microscopy, high-resolution 3-dimensional image analysis, and computational fluid dynamics simulation. We then performed molecular and functional assays in patient-derived cardiac fibroblasts based on YAP (yes-associated protein)-transcriptional enhanced associate domain (TEAD) mechanosensing activity and collagen contraction assays. The analysis of HF decellularized ECM resulting from ischemic or dilated cardiomyopathy, as well as from mouse infarcted tissue, identified a common pattern of modifications in their 3-dimensional topography. As compared with healthy heart, HF ECM exhibited aligned, flat, and compact fiber bundles, with reduced elasticity and organizational complexity. At the molecular level, RNA sequencing of HF cardiac fibroblasts highlighted the overrepresentation of dysregulated genes involved in ECM organization, or being connected to TGFβ1 (transforming growth factor β1), interleukin-1, TNF-α, and BDNF signaling pathways. Functional tests performed on HF cardiac fibroblasts pointed at mechanosensor YAP as a key player in ECM remodeling in the diseased heart via transcriptional activation of focal adhesion assembly. Finally, in vitro experiments clarified pathological cardiac ECM prevents cell homing, thus providing further hints to identify a possible window of action for cell therapy in cardiac diseases. CONCLUSIONS: Our multiparametric approach has highlighted repercussions of ECM remodeling on cell homing, cardiac fibroblast activation, and focal adhesion protein expression via hyperactivated YAP signaling during HF.

• MeSH
• adaptorové proteiny signální transdukční genetika   metabolismus   MeSH
• buněčný převod mechanických signálů MeSH
• dilatační kardiomyopatie genetika   metabolismus   patologie   patofyziologie   MeSH
• extracelulární matrix genetika   metabolismus   ultrastruktura   MeSH
• fibroblasty metabolismus   ultrastruktura   MeSH
• funkce levé komory srdeční * MeSH
• infarkt myokardu genetika   metabolismus   patologie   patofyziologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   ultrastruktura   MeSH
• myši inbrední C57BL MeSH
• pohyb buněk MeSH
• remodelace komor * MeSH
• srdeční selhání genetika   metabolismus   patologie   patofyziologie   MeSH
• studie případů a kontrol MeSH
• transkripční faktory genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• audiovizuální média MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The rate of reparative osteogenesis controls when an implant is sufficiently stable as to allow functional loading. Using a mini pig model, the rate of reparative osteogenesis in two types of implant sites for example, an osteotomy versus a fresh extraction socket were compared. METHODS: Eight adult mini pigs were used for the study. In phase I, three premolars were extracted on one side of the oral cavity; 12 weeks later, in phase II, osteotomies were produced in healed extraction sites, and contralateral premolars were extracted. Animals were sacrificed 1, 5, and 12 weeks after phase II. Bone repair and remodeling were evaluated using quantitative micro-computed tomographic imaging, histology, and histochemical assays coupled with quantitative dynamic histomorphometry. RESULTS: One week after surgery, extraction sockets and osteotomy sites exhibited similar patterns of new bone deposition. Five weeks after surgery, mineral apposition rates (MARs) were elevated at the injury sites relative to intact bone. Twelve weeks after surgery, the density of new bone in both injury sites was equivalent to intact bone but quantitative dynamic histomorphometry and cellular activity assays demonstrated bone remodeling was still underway. CONCLUSIONS: The mechanisms and rates of reparative osteogenesis were equivalent between fresh extraction sockets and osteotomies. The volume of new bone required to fill a socket, however, was significantly greater than the volume required to fill an osteotomy. These data provide a framework for estimating the rate of reparative osteogenesis and the time to loading of implants placed in healed sites versus fresh extraction sockets.

• MeSH
• endoseální implantace zubů metody   MeSH
• extrakce zubů metody   MeSH
• miniaturní prasata MeSH
• prasata MeSH
• premolár chirurgie   MeSH
• remodelace kosti MeSH
• zubní implantáty * MeSH
• zubní lůžko * diagnostické zobrazování   chirurgie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH