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Segmentation helps interpret imaging data in a biological context. With the development of powerful tools for automated segmentation, public repositories for imaging data have added support for sharing and visualizing segmentations, creating the need for interactive web-based visualization of 3D volume segmentations. To address the ongoing challenge of integrating and visualizing multimodal data, we developed Mol* Volumes and Segmentations (Mol*VS), which enables the interactive, web-based visualization of cellular imaging data supported by macromolecular data and biological annotations. Mol*VS is fully integrated into Mol* Viewer, which is already used for visualization by several public repositories. All EMDB and EMPIAR entries with segmentation datasets are accessible via Mol*VS, which supports the visualization of data from a wide range of electron and light microscopy experiments. Additionally, users can run a local instance of Mol*VS to visualize and share custom datasets in generic or application-specific formats including volumes in .ccp4, .mrc, and .map, and segmentations in EMDB-SFF .hff, Amira .am, iMod .mod, and Segger .seg. Mol*VS is open source and freely available at https://molstarvolseg.ncbr.muni.cz/.

Summary Every protein family has a set of characteristic secondary structures. However, due to individual variations, a single structure is not enough to represent the whole family. OverProt can create a secondary structure consensus, showing the general fold of the family as well as its variation. Our server provides precomputed results for all CATH superfamilies and user-defined computations, visualized by an interactive viewer, which shows the secondary structure element type, length, frequency of occurrence, spatial variability and β-connectivity. Availability and implementation OverProt Server is freely available at https://overprot.ncbr.muni.cz. Supplementary information Supplementary data are available at Bioinformatics online.

Motivation Protein structural families are groups of homologous proteins defined by the organization of secondary structure elements (SSEs). Nowadays, many families contain vast numbers of homologous structures and the SSEs can help to orient within them. Communities around specific protein families have even developed specialized SSE annotations, assigning always the same name to the equivalent SSEs in homologous proteins. A detailed analysis of the groups of equivalent SSEs and their variability provides an overview of the studied protein family and can be used to enrich the analysis of a particular protein at hand. Results We developed a workflow for analysis of the secondary structure anatomy of a protein family, based on SSE annotation tool SecStrAnnotator. We applied this analysis to the model family of cytochromes P450 (CYPs) – a family of important biotransformation enzymes with a community-wide used SSE annotation. We report the occurrence, typical length and amino acid sequence for the equivalent SSE groups, as well as the conservation/variability of these properties. We also suggest a generic residue numbering scheme for the CYP family. The comparison between the bacterial and eukaryotic part of the family highlights the major differences and reveals an anomalous group of bacterial CYPs with some typically eukaryotic features. This hints at possible evolutionary and functional relationships. Availability The software and data are available at https://webchem.ncbr.muni.cz/Wiki/SecStrAnnotator Contact radka.svobodova@ceitec.muni.cz , karel.berka@upol.cz

We report an experimental study of oscillatory thermal counterflow of superfluid $^{4}\mathrm{He}$ and its transition to quantum turbulence inspired by the work of Kotsubo and Swift [Phys. Rev. Lett. 62, 2604 (1989)]. We use a pair of transversally oriented second-sound sensors to provide direct proof that upon exceeding a critical heat flux, quantized vorticity is generated in the antinodes of the longitudinal resonances of the oscillating counterflow. Building on modern understanding of oscillatory flows of superfluid $^{4}\mathrm{He}$ [D. Schmoranzer et al., Phys. Rev. B 99, 054511 (2019)], we re-evaluate the original data together with ours and provide grounds for the previously unexplained temperature dependence of critical velocities. Our analysis incorporates a classical flow instability in the normal component described by the dimensionless Donnelly number, which is shown to trigger quantum turbulence at temperatures below $\ensuremath{\approx}1.7\phantom{\rule{0.16em}{0ex}}\mathrm{K}$. This contrasts with the original interpretation based on the dynamics of quantized vortices, and we show that for oscillatory counterflow, such an approach is valid only at temperatures above $\ensuremath{\approx}1.8\phantom{\rule{0.16em}{0ex}}\mathrm{K}$. Finally, we demonstrate that the instabilities occurring in oscillatory counterflow are governed by the same underlying physics as those in flow due to submerged oscillators and propose a unified description of high Stokes number coflow and counterflow experiments.

Quantum turbulence—the stochastic motion of quantum fluids such as 4 He and 3 He-B, which display pure superfluidity at zero temperature and two-fluid behavior at finite but low temperatures—has been a subject of intense experimental, theoretical, and numerical studies over the last half a century. Yet, there does not exist a satisfactory phenomenological framework that captures the rich variety of experimental observations, physical properties, and characteristic features, at the same level of detail as incompressible turbulence in conventional viscous fluids. Here we present such a phenomenology that captures in simple terms many known features and regimes of quantum turbulence, in both the limit of zero temperature and the temperature range of two-fluid behavior.

Superconducting heat switches with extremely low normal state resistances are needed for constructing continuous nuclear demagnetization refrigerators with high cooling power. Aluminum is a suitable superconductor for the heat switch because of its high Debye temperature and its commercial availability in high purity. We have constructed a high quality Al heat switch whose design is significantly different than that of previous heat switches. In order to join the Al to Cu with low contact resistance, we plasma etched the Al to remove its oxide layer then immediately deposited Au without breaking the vacuum of the e-beam evaporator. In the normal state of the heat switch, we measured a thermal conductance of $8 T$ W/K$^2$ which is equivalent to an electrical resistance of 3 n$Ω$ according to the Wiedemann-Franz law. In the superconducting state we measured a thermal conductance that is $2\times10^6$ times lower than that of the normal state at 50 mK.

Sanguinarine is a benzo[c]phenanthridine alkaloid with interesting cytotoxic properties, such as induction of oxidative DNA damage and very rapid apoptosis, which is not mediated by p53-dependent signaling. It has been previously documented that sanguinarine is reduced with NADH even in absence of any enzymes while being converted to its dihydro form. We found that the dark blue fluorescent species, observed during sanguinarine reduction with NADH and misinterpreted by Matkar et al. (Arch. Biochem. Biophys. 2008, 477, 43–52) as an anionic form of the alkaloid, is a covalent adduct formed by the interaction of NADH and sanguinarine. The covalent adduct is then converted slowly to the products, dihydrosanguinarine and NAD+, in the second step of reduction. The product of the reduction, dihydrosanguinarine, was continually re-oxidized by the atmospheric oxygen back to sanguinarine, resulting in further reacting with NADH and eventually depleting all NADH molecules. The ability of sanguinarine to diminish the pool of NADH and NADPH is further considered when explaining the sanguinarine-induced apoptosis in living cells.

LiteMol suite is an innovative solution that enables near-instant delivery of model and experimental biomacromolecular structural data, providing users with an interactive and responsive experience in all modern web browsers and mobile devices. LiteMol suite is a combination of data delivery services (CoordinateServer and DensityServer), compression format (BinaryCIF), and a molecular viewer (LiteMol Viewer). The LiteMol suite is integrated into Protein Data Bank in Europe (PDBe) and other life science web applications (e.g., UniProt, Ensemble, SIB, and CNRS services), it is freely available at https://litemol.org , and its source code is available via GitHub. LiteMol suite provides advanced functionality (annotations and their visualization, powerful selection features), and this chapter will describe their use for visual inspection of protein structures.

LiteMol suite is an innovative solution that enables near-instant delivery of model and experimental biomacromolecular structural data, providing users with an interactive and responsive experience in all modern web browsers and mobile devices. LiteMol suite is a combination of data delivery services (CoordinateServer and DensityServer), compression format (BinaryCIF), and a molecular viewer (LiteMol Viewer). The LiteMol suite is integrated into Protein Data Bank in Europe (PDBe) and other life science web applications (e.g., UniProt, Ensemble, SIB, and CNRS services), it is freely available at https://litemol.org , and its source code is available via GitHub. LiteMol suite provides advanced functionality (annotations and their visualization, powerful selection features), and this chapter will describe their use for visual inspection of protein structures.

Secondary structure elements (SSEs) are inherent parts of protein structures, and their arrangement is characteristic for each protein family. Therefore, annotation of SSEs can facilitate orientation in the vast number of homologous structures which is now available for many protein families. It also provides a way to identify and annotate the key regions, like active sites and channels, and subsequently answer the key research questions, such as understanding of molecular function and its variability.This chapter introduces the concept of SSE annotation and describes the workflow for obtaining SSE annotation for the members of a selected protein family using program SecStrAnnotator.

Secondary structure elements (SSEs) are inherent parts of protein structures, and their arrangement is characteristic for each protein family. Therefore, annotation of SSEs can facilitate orientation in the vast number of homologous structures which is now available for many protein families. It also provides a way to identify and annotate the key regions, like active sites and channels, and subsequently answer the key research questions, such as understanding of molecular function and its variability. This chapter introduces the concept of SSE annotation and describes the workflow for obtaining SSE annotation for the members of a selected protein family using program SecStrAnnotator.

Selected benzo[c]phenathridine alkaloids were biotransformed using rat liver microsomes and identified by liquid chromatography and mass spectrometry. While the metabolites of commercially available sanguinarine and chelerythrine have been studied in detail, data about the metabolism of the minor alkaloids remained unknown. Reactions involved in transformation include single and/or double O-demethylation, demethylenation, reduction, and hydroxylation. Two metabolites, when isolated, purified and tested for toxicity, were found to be less toxic than the original compounds.

Eisenia lucens is an earthworm living in the organic soil layer of decomposing wood. When irritated, the worm expels coelomic fluid through pores in its body wall, exhibiting blue-green bioluminescence. The mechanism of the bioluminescence, which seems to be different from other bioluminescence systems of terrestrial animals, has been studied in this work. Many lines of evidence indicate that riboflavin stored in coelomycetes plays an important role in this glowing reaction.

Composition and organization of secondary structure elements (SSEs), such as alpha-helices and beta-sheets, are characteristic for protein families and they participate in formation of protein fold. They are however often influenced by the sequence variability and ligand binding. For this reason, identification of similarities and differences between SSEs can help us in the analysis of individual proteins within a protein family. To utilize the SSEs for research of individual protein families, we need to have the SSEs easily and automatically intercomparable within one protein family. Specifically, the corresponding SSEs should have the same name (annotation) and there should be a transparent schema of their localization in the protein structures. Unfortunately, SSE annotations are still performed mainly manually and universal automatic approach to assign SSE names is not available yet. Moreover, current methods focused on 2D visualization of SSEs (e.g., PROMOTIF, Pro-origami, HERA) do not consider information about real distances of SSEs. Therefore, even when two proteins from the same family differ only slightly, their SSE 2D diagrams can be totally different. For this reason, we developed a tool set which can perform SSE annotation and 2D visualization in such a way that structural information is kept. Applicability of this approach is shown in a case study focused on cytochromes P450. This protein family of drug-metabolizing enzymes has currently available more than 750 structures from about 30 organisms and each cytochrome P450 contains more than 20 SSEs for which there is a stable annotation used through the community. Our approach can be further extended to other protein structural families, which will allow family-wide SSE annotations and comparisons in a simple visual manner.

We present the LiteMol suite, a tool for visualizing large macromolecular structure data sets that is freely available at https://www.litemol.org.

Recent advances in Cryo-EM and other structure determination techniques enabled a rapid increase in the complexity and size of biomacromolecular structures available in the Protein Data Bank (PDB). A great challenge is to deliver and visualize this data to the user in a reasonable time. Until now, Java-based applets such as Jmol have served this purpose. However, the lack of support for Java applets in the web browsers and introduction of HTML5 and WebGL web frameworks provide an opportunity to develop better solutions to address this problem.We have developed a comprehensive solution for both efficient delivery of large data sets and interactive visualisation of macromolecular structures.The CoordinateServer (https://www.ebi.ac.uk/pdbe/coordinates) provides functionality for dynamic selection of a subset of structural data (backbone, ligand binding sites, etc.) that is of interest to the user. The amount of transferred data is further reduced using binary representation of the standard mmCIF data format called BinaryCIF. The CoordinateServer thus provides a complete solution for efficient transfer of data to user interface.LiteMol (http://ncbr.muni.cz/LiteMol) is an interactive browser based 3D viewer, designed using HTML5 and WebGL technologies that provides all key structural visualisation modes. The viewer also integrates PDBe REST API services (http://pdbe.org/api) to show biomacromolecular annotations (validation, sequence annotation). LiteMol can use the standard mmCIF files or the CoordinateServer for fast data access. Thanks to integration with the CoordinateServer, LiteMol can generate an interactive 3D display for the largest currently available structure, the HIV capsid with 2.4 million atoms, in less than a minute. LiteMol is integrated into PDBe entry pages (e.g. http://www.ebi.ac.uk/pdbe/entry/pdb/1cbs/bound/REA) and can, for the first time, show the electron density maps online in an interactive way. We are collaborating with UniProt, OpenTargets, and Glycopedia teams to integrate LiteMol into their pages.