Fungal Immunomodulatory Proteins from Ganoderma species (gFIPs) have garnered significant interest due to their potential therapeutic applications in modulating immune responses. This study investigates the sequence, structural, and functional relationships of gFIPs with other proteins involved in immune modulation. Utilizing molecular modelling, multiple sequence alignments, and structural superimposition, we analysed two FIP crystallized structures (PDB IDs: 3F3H and 3KCW) alongside homologous sequences from various taxonomic groups. Our results reveal conserved motifs across fungal, bacterial, and human sequences, indicating potential functional similarities. Comparative structural analysis highlights significant conservation in FIP architecture, with variations primarily in the N-terminal regions. Notably, structural alignment with bacterial toxins, such as ADP-ribosylating binary toxin from Clostridium difficile or protective antigen of Anthrax toxin from Bacillus anthracis suggests mechanistic insights into FIP's immunomodulatory actions. Structural similarities between gFIPs and immune-related proteins, such as bacterial toxin-binding domains, antibody fragments, T-cell receptor components, and immune checkpoint regulators (PD-1) suggest their potential involvement in immune response/inflammation signalling pathways. This comprehensive analysis elucidates the structural basis for the diverse biological activities of gFIPs and underscores their potential as therapeutic agents in immune-related diseases.
Using three-dimensional scans of human faces has become an emerging technique in studies of human variation, where the quantitative assessment of facial similarity complements the measurement of other somatic traits. While the algorithms for automated registration (geometrical alignment) and similarity measurement of two facial scans are well-known and used in practice, their direct application for batch processing is limited due to computational requirements. The batch N:N analysis, where all pairs of scans in a dataset must be mutually registered and compared, introduces quadratic complexity with computation times reaching hours even for relatively small datasets, making it practically unusable. This paper presents a rapid and accurate approach with nearly linear time complexity. Our solution utilizes properties of facial scan geometry to optimize individual steps. Moreover, the algorithm deals with possible holes and other artifacts in polygonal meshes automatically. Experiments demonstrate that the proposed solution is very fast and sufficiently accurate compared to a precise quadratic-time baseline approach.
- MeSH
- Algorithms MeSH
- Humans MeSH
- Face * anatomy & histology MeSH
- Image Processing, Computer-Assisted methods MeSH
- Imaging, Three-Dimensional * methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Over the past decade, advances in electron diffraction (ED) have significantly improved the determination and refinement of crystal structures, making it a viable alternative to traditional X-ray diffraction (XRD), especially for very small volumes, such as nanoparticles (NPs). This work evaluates the application of advanced 3D ED techniques to the analysis of isolated NPs, focusing on their efficacy and limitations in terms of crystal size and accuracy of results. Our investigation begins by addressing the challenges of obtaining 3D ED data for NPs, including sample preparation, instrument capabilities, and the choice of 3D ED methods. We find that 3D ED can provide highly accurate structure refinements for crystals in the 50-100 nm range and is also effective for the analysis of NPs as small as 10 nm. While kinematical approximations often provide accurate refinements similar to those obtained from powder XRD, the accuracy depends on the specific data set and may not always align with traditional reliability indicators. Our study shows that dynamical scattering effects, even in tiny crystals, challenge the assumption that they are negligible in thin crystal scenarios. Addressing these effects through full dynamical refinement significantly improves the accuracy and reliability of the structure determination. This report suggests a paradigm shift in viewing dynamic scattering effects not as mere obstacles but as opportunities to explore crystal structures in greater detail on smaller scales. By embracing these complexities, 3D ED can provide precise and reliable structural insights that are critical to the advancement of nanotechnology and materials science.
- Keywords
- crystallography, dynamical refinement, electron diffraction, electron microscopy, oxide nanoparticles,
- Publication type
- Journal Article MeSH
Interleukin-2-inducible T-cell kinase (ITK) and Bruton's tyrosine kinase (BTK) are two important members of the Tec family with crucial roles in immune system function. Deregulation in ITK and BTK activity is linked to several hematological malignancies, making them key targets for cancer immunotherapy. In this study, we synthesized a series of azaspirooxindolinone derivatives and evaluated their cytotoxic activity against ITK/BTK-negative and positive cancer cell lines, followed by enzymatic inhibition studies to assess the ITK/BTK kinase selectivity of two hit compounds. Several compounds demonstrated selective cytotoxicity against ITK- or BTK-expressing cells. Compound 3d exhibited high cytotoxicity in ITK-positive Jurkat (IC50 = 3.58 µM) and BTK-positive Ramos (IC50 = 3.06 µM) cells, while compound 3j showed strong cytotoxicity in Ramos (IC50 = 1.38 µM) and Jurkat (IC50 = 4.16 µM) cells. Compounds 3a and 3e were selectively cytotoxic in Jurkat cells (IC50 = 9.36 µM and 10.85 µM, respectively), while compounds 3f and 3g were highly cytotoxic in Ramos cells (IC50 = 1.82 µM and 1.42 µM, respectively). None of the active compounds exhibited cytotoxicity in non-cancer cell lines (IC50 > 50 µM), demonstrating their selectivity for malignant cells. Enzyme inhibition assay showed that 3d is a selective ITK inhibitor (IC50 = 0.91 µM) with no detectable BTK inhibition, aligning with its strong activity in ITK-positive cells. In contrast, compound 3j did not inhibit ITK or BTK enzymatically, suggesting an alternative mechanism of action. These findings highlight 3d as a promising ITK inhibitor and warrant further investigation to elucidate its mechanism of action.
- Keywords
- Anti-cancer derivatives, Azaspirooxindolinones, Bruton’s tyrosine kinase, Interleukin-2-inducible T-cell kinase, Molecular docking,
- MeSH
- Protein Kinase Inhibitors * pharmacology chemical synthesis chemistry MeSH
- Humans MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Oxindoles pharmacology chemistry chemical synthesis MeSH
- Cell Proliferation drug effects MeSH
- Agammaglobulinaemia Tyrosine Kinase * antagonists & inhibitors metabolism MeSH
- Antineoplastic Agents * pharmacology chemical synthesis chemistry MeSH
- Drug Design * MeSH
- Drug Screening Assays, Antitumor * MeSH
- Molecular Docking Simulation MeSH
- Spiro Compounds chemistry pharmacology chemical synthesis MeSH
- Protein-Tyrosine Kinases * antagonists & inhibitors metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- BTK protein, human MeSH Browser
- emt protein-tyrosine kinase MeSH Browser
- Protein Kinase Inhibitors * MeSH
- Oxindoles MeSH
- Agammaglobulinaemia Tyrosine Kinase * MeSH
- Antineoplastic Agents * MeSH
- Spiro Compounds MeSH
- Protein-Tyrosine Kinases * MeSH
OBJECTIVE: We propose a method utilizing mixed reality (MR) goggles (HoloLens 2, Microsoft) to facilitate impacted canine alignment, as planning the traction direction and force delivery could benefit from 3D data visualization using mixed reality (MR). METHODS: Cone-beam CT scans featuring isometric resolution and low noise-to-signal ratio were semi-automatically segmented in Inobitec software. The exported 3D mesh (OBJ file) was then optimized for the HoloLens 2. Using the Unreal Engine environment, we developed an application for the HoloLens 2, implementing HoloLens SDK and UX Tools. Adjustable pointers were added for planning attachment placement, traction direction, and point of force application. The visualization was presented to participants of a course on impacted teeth treatment, followed by a 10-question survey addressing potential advantages (5-point scale: 1 = totally agree, 5 = totally disagree). RESULTS: Out of 38 respondents, 44.7% were orthodontists, 34.2% dentists, 15.8% dental students, and 5.3% dental technicians. Most respondents (44.7%) were between 35 and 44 years old, and only 1 (2.6%) respondent was 55-64 years old. Median answers for six questions were 'totally agree' (25th percentile 1, 75th percentile 2) and for four questions 'agree' (25th percentile 1, 75th percentile 2). No correlation was found between age, profession, and responses. CONCLUSION: Our method generated substantial interest among clinicians. The initial responses affirm the potential benefits, supporting the continued exploration of MR-based techniques for the treatment of impacted teeth. However, the recommendation for widespread use awaits validation through clinical trials.
- Keywords
- AR, HoloLens 2 goggles, VR, impacted canine, mixed virtual reality,
- MeSH
- Augmented Reality MeSH
- Adult MeSH
- Humans MeSH
- Proof of Concept Study MeSH
- Patient Care Planning * MeSH
- Cone-Beam Computed Tomography * methods MeSH
- Software MeSH
- Cuspid diagnostic imaging MeSH
- Tooth, Impacted * diagnostic imaging therapy MeSH
- Imaging, Three-Dimensional * methods MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Inherently chiral compounds, such as calixarenes, are chiral due to a nonplanar three-dimensional (3D) structure. Determining their conformation is essential to understand their properties, with nuclear magnetic resonance (NMR) spectroscopy being one applicable method. Using alignment media to measure residual dipolar couplings (RDCs) to obtain structural information is advantageous when classical NMR parameters like the nuclear Overhauser effect (NOE) or J-couplings fail. Besides providing more accurate structural information, the alignment media can induce different orientations of enantiomers. In this study, we examined the ability of polyglutamates with different side-chain moieties─poly-γ-benzyl-l-glutamate (PBLG) and poly-γ-p-biphenylmethyl-l-glutamate (PBPMLG) ─to enantiodifferentiate the inherently chiral phenoxathiin-based thiacalix[4]arenes. Both media, in combination with two solvents, allowed for enantiodiscrimination, which was, to the best of our knowledge, proved for the first time on inherently chiral compounds. Moreover, using the experimental RDCs, we investigated the calix[4]arenes conformational preferences in solution, quantitatively analyzed the differences in the alignment of the enantiomers, and discussed the pitfalls of the use of the RDC analysis.
- Publication type
- Journal Article MeSH
Inkjet printing of liquid crystal (LC) microlens arrays is particularly appealing for the development of switchable 2D/3D organic light-emitting diode (OLED) displays, as the printing process ensures that the lenses can be deposited directly and on-demand onto the pixelated OLED layer without the need for additional steps, thus simplifying fabrication complexity. Even if different fabrication technologies have been employed and good results in LC direct printing have already been achieved, all the systems used require costly equipment and heated nozzles to reduce the LC solution's viscosity. Here, we present the direct printing of a nematic LC (NLC) lens by a Drop-on-Demand (DoD) inkjet printing by a pyro-electrohydrodynamic effect for the first time. The method works at ambient temperature and avoids dispensing nozzles, thus offering a noncontact manipulation approach of liquid with high resolution and good repeatability on different kinds of substrates. NLC microlenses are printed on different substrates and fully characterized. Polarization properties are evaluated for various samples, i.e., NLC lenses on unaligned and indium-tin oxide (ITO) aligned. Moreover, an in-depth characterization of the NLC lenses is reported by polarized optical microscopy and by analyzing the birefringence in digital holographic microscopy.
- Keywords
- inkjet printing, liquid crystal, microlenses, polarized optical microscope, pyro-electrohydrodynamic,
- Publication type
- Journal Article MeSH
Geophysics aims to locate bodies with varying density. We discovered an innovative approach for estimation of the location, in particular depth of a causative body, based on its relative horizontal dimensions, using a dimensionality indicator (I). The method divides the causative bodies into two types based on their horizontal spread: line of poles and point pole (LOP-PP) category, and line of poles and plane of poles (LOP-POP) category; such division allows for two distinct solutions. The method's depth estimate relates to the relative variations of the causative body's horizontal extent and leads to the solutions of the Euler Deconvolution method in specific cases. For causative bodies with limited and small depth extent, the estimated depth (z^0) corresponds to the center of mass, while for those with a large depth extent, z^0 relates to the center of top surface. Both the depth extent and the dimensionality of the causative body influence the depth estimates. As the depth extent increases, the influence of I on the estimated depth is more pronounced. Furthermore, the behavior of z^0 exhibits lower errors for larger values of I in LOP-POP solutions compared with LOP-PP solutions. We tested several specific model scenarios, including isolated and interfering sources with and without artificial noise. We also tested our approach on real lunar data containing two substantial linear structures and their surrounding impact basins and compared our results with the Euler deconvolution method. The lunar results align well with geology, supporting the effectiveness of this approach. The only assumption in this method is that we should choose between whether the gravity signal originates from a body within the LOP-PP category or the LOP-POP category. The depth estimation requires just one data point. Moreover, the method excels in accurately estimating the depth of anomalous causative bodies across a broad spectrum of dimensionality, from 2 to 3D. Furthermore, this approach is mathematically straightforward and reliable. As a result, it provides an efficient means of depth estimation for anomalous bodies, delivering insights into subsurface structures applicable in both planetary and engineering domains.
- Publication type
- Journal Article MeSH
Morpheeins are proteins that adapt their morphology and function to the environment. Therefore, their use in nanotechnology opens up the bottom-up preparation of anisotropic metamaterials, based on the sequential use of different stimuli. A prominent member of this family of proteins is peroxiredoxins (Prx), with dual peroxidase and chaperone function, depending on the pH of the media. At high pH, they show a toroidal morphology that turns into tubular stacks upon acidification. While the toroidal conformers have been explored as building blocks to yield 1D and 2D structures, the obtention of higher ordered materials remain unexplored. In this research, the morpheein behaviour of Prx is exploited to yield columnar aggregates, that are subsequently self-assembled into 3D anisotropic bundles. This is achieved by electrostatic recognition between the negatively charged protein rim and a positively charged porphyrin acting as molecular glue. The subsequent and orthogonal input lead to the alignment of the monodimensional stacks side-by-side, leading to the precise assembly of this anisotropic materials.
- MeSH
- Hydrogen-Ion Concentration MeSH
- Nanotechnology MeSH
- Peroxidase * metabolism MeSH
- Peroxiredoxins * chemistry metabolism MeSH
- Static Electricity MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Peroxidase * MeSH
- Peroxiredoxins * MeSH
