Neurotropic pathogens, notably, herpesviruses, have been associated with significant neuropsychiatric effects. As a group, these pathogens can exploit molecular mimicry mechanisms to manipulate the host central nervous system to their advantage. Here, we present a systematic computational approach that may ultimately be used to unravel protein-protein interactions and molecular mimicry processes that have not yet been solved experimentally. Toward this end, we validate this approach by replicating a set of pre-existing experimental findings that document the structural and functional similarities shared by the human cytomegalovirus-encoded UL144 glycoprotein and human tumor necrosis factor receptor superfamily member 14 (TNFRSF14). We began with a thorough exploration of the Homo sapiens protein database using the Basic Local Alignment Search Tool (BLASTx) to identify proteins sharing sequence homology with UL144. Subsequently, we used AlphaFold2 to predict the independent three-dimensional structures of UL144 and TNFRSF14. This was followed by a comprehensive structural comparison facilitated by Distance-Matrix Alignment and Foldseek. Finally, we used AlphaFold-multimer and PPIscreenML to elucidate potential protein complexes and confirm the predicted binding activities of both UL144 and TNFRSF14. We then used our in silico approach to replicate the experimental finding that revealed TNFRSF14 binding to both B- and T-lymphocyte attenuator (BTLA) and glycoprotein domain and UL144 binding to BTLA alone. This computational framework offers promise in identifying structural similarities and interactions between pathogen-encoded proteins and their host counterparts. This information will provide valuable insights into the cognitive mechanisms underlying the neuropsychiatric effects of viral infections.

• Klíčová slova
• Bioinformatics, Cognition, Mitochondria, Psychiatry, Virus,
• MeSH
• kognice fyziologie   MeSH
• lidé MeSH
• molekulární mimikry * MeSH
• molekulární modely MeSH
• sekvence aminokyselin MeSH
• vazba proteinů MeSH
• virové proteiny metabolismus   chemie   MeSH
• výpočetní biologie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• virové proteiny MeSH

The eIF4F translation initiation complex plays a critical role in melanoma resistance to clinical BRAF and MEK inhibitors. In this study, we uncover a function of eIF4F in the negative regulation of the rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling pathway. We demonstrate that eIF4F is essential for controlling ERK signaling intensity in treatment-naïve melanoma cells harboring BRAF or NRAS mutations. Specifically, the dual-specificity phosphatase DUSP6/MKP3, which acts as a negative feedback regulator of ERK activity, requires continuous production in an eIF4F-dependent manner to limit excessive ERK signaling driven by oncogenic RAF/RAS mutations. Treatment with small-molecule eIF4F inhibitors disrupts the negative feedback control of MAPK signaling, leading to ERK hyperactivation and EGR1 overexpression in melanoma cells in vitro and in vivo. Furthermore, our quantitative analyses reveal a high spare signaling capacity in the ERK pathway, suggesting that eIF4F-dependent feedback keeps the majority of ERK molecules inactive under normal conditions. Overall, our findings highlight the crucial role of eIF4F in regulating ERK signaling flux and suggest that pharmacological eIF4F inhibitors can disrupt the negative feedback control of MAPK activity in melanomas with BRAF and NRAS activating mutations.

• Klíčová slova
• DUSP6, ERK, MAP kinase, eIF4F, melanoma,
• MeSH
• eukaryotický iniciační faktor 4F * metabolismus   genetika   MeSH
• extracelulárním signálem regulované MAP kinasy metabolismus   MeSH
• fosfatasa 6 s dvojí specificitou metabolismus   genetika   MeSH
• GTP-fosfohydrolasy * metabolismus   genetika   MeSH
• lidé MeSH
• MAP kinasový signální systém * genetika   MeSH
• melanom * genetika   metabolismus   patologie   MeSH
• membránové proteiny * metabolismus   genetika   MeSH
• mutace * MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• protoonkogenní proteiny B-Raf * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• DUSP6 protein, human MeSH Prohlížeč
• EIF4E protein, human MeSH Prohlížeč
• eukaryotický iniciační faktor 4F * MeSH
• extracelulárním signálem regulované MAP kinasy MeSH
• fosfatasa 6 s dvojí specificitou MeSH
• GTP-fosfohydrolasy * MeSH
• membránové proteiny * MeSH
• NRAS protein, human MeSH Prohlížeč
• protoonkogenní proteiny B-Raf * MeSH

Syncytin-1, a human fusogenic protein of retroviral origin, is crucial for placental syncytiotrophoblast formation. To mediate cell-to-cell fusion, Syncytin-1 requires specific interaction with its cognate receptor. Two trimeric transmembrane proteins, Alanine, Serine, Cysteine Transporters 1 and 2 (ASCT1 and ASCT2), were suggested and widely accepted as Syncytin-1 cellular receptors. To quantitatively assess the individual contributions of human ASCT1 and ASCT2 to the fusogenic activity of Syncytin-1, we developed a model system where the ASCT1 and ASCT2 double knockout was rescued by ectopic expression of either ASCT1 or ASCT2. We demonstrated that ASCT2 was required for Syncytin-1 binding, cellular entry, and cell-to-cell fusion, while ASCT1 was not involved in this receptor interaction. We experimentally validated the ASCT1-ASCT2 heterotrimers as a possible explanation for the previous misidentification of ASCT1 as a receptor for Syncytin-1. This redefinition of receptor specificity is important for proper understanding of Syncytin-1 function in normal and pathological pregnancy.

• Klíčová slova
• Syncytin-1, cell-to-cell fusion, endogenous retrovirus, placenta, viral receptor,
• MeSH
• antigeny CD98 - těžký řetězec MeSH
• fúze buněk * MeSH
• genové produkty env * metabolismus   genetika   MeSH
• lidé MeSH
• placenta * metabolismus   MeSH
• těhotenské proteiny * metabolismus   genetika   MeSH
• těhotenství MeSH
• transportní systém ASC pro aminokyseliny * metabolismus   genetika   MeSH
• transportní systémy pro neutrální aminokyseliny metabolismus   genetika   MeSH
• trofoblasty metabolismus   cytologie   MeSH
• vedlejší histokompatibilní antigeny metabolismus   genetika   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD98 - těžký řetězec MeSH
• genové produkty env * MeSH
• SLC1A5 protein, human MeSH Prohlížeč
• SLC3A2 protein, human MeSH Prohlížeč
• syncytin MeSH Prohlížeč
• těhotenské proteiny * MeSH
• transportní systém ASC pro aminokyseliny * MeSH
• transportní systémy pro neutrální aminokyseliny MeSH
• vedlejší histokompatibilní antigeny MeSH

The acoustic wave produced alongside laser-induced plasmas can be used in conjunction with the recorded atomic spectra of plasma emission to expand the physicochemical information acquired from a single inspection event. Among the most interesting uses of acoustic information is the differentiation of mineral phases with similar optical responses coexisting in geological targets. In addition, laser-induced plasma acoustics (LIPAc) can provide data related to the inspected material's hardness, density, and compactness. In this paper, we present a dual acoustic-optic laser-based strategy for the generation of high-resolution surface images of mineral samples. By combining simultaneous multimodal LIBS (laser-induced breakdown spectroscopy) and LIPAc spectral data from laser-induced plasmas, we explore the mineralogical composition of rocks embedded in resin matrixes to distinguish their chemical composition as well as their crystal phases based on physical changes caused by the different spatial arrangements of the constituent atoms. The multispectral polyhedron created by merging singular optical maps, one per detected elements, and the coincidental acoustic map enhance the distinction between regions present within the matrix of a host rock as compared to the differentiation yielded by each technique when used separately. The chemical information guides the composition of the mineral phases in the host rock. Then, the physical information obtained from acoustics may reinforce the identification of the detected mineral phase, draw the geological history of the inspected section, and showcase possible transformations, mainly of polymorphic nature. To test the combination proposed herein, we also inspected a septarian nodule featuring an ensemble of mineral phases with different origins. Mixed optical and acoustic responses from laser-produced plasmas of this complex sample allowed us to obtain more specific information. This approach constitutes a reliable and high-throughput tool for studying the surface of geological samples, which can substantially supplement well-established techniques for mineralogical analysis such as Raman spectroscopy and X-ray diffraction.

• Publikační typ
• časopisecké články MeSH

Dissolved organic matter (DOM) is an ultracomplex mixture that plays a central role in global biogeochemical cycles. Despite its importance, DOM remains poorly understood at the molecular level. Over the last decades, significant efforts have been made to decipher the chemical composition of DOM by high-resolution mass spectrometry (HR-MS) and liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS). Yet, the complexity and high degree of nonresolved isomers still hamper the full structural analysis of DOM. To address this challenge, we developed an offline two-dimensional (2D) LC approach using two reversed-phase dimensions with orthogonal pH levels, followed by MS/MS data acquisition and molecular networking. 2D-LC-MS/MS reduced the complexity of DOM, enhancing the quality of MS/MS spectra and increasing spectral annotation rates. Applying our approach to analyze coastal-surface DOM from Southern California (USA) and open-ocean DOM from the central North Pacific (Hawaii), we annotated in total more than 600 structures via MS/MS spectrum matching, which was up to 90% more than that in iterative 1D LC-MS/MS analysis with the same total run time. Our data offer unprecedented insights into the molecular composition of marine DOM and highlight the potential of 2D-LC-MS/MS approaches to decipher the chemical composition of ultracomplex samples.

• Klíčová slova
• 2D chromatography, 2D-LC-MS/MS, dissolved organic matter, environmental metabolomics, molecular networking, tandem mass spectrometry,
• MeSH
• chromatografie kapalinová MeSH
• metabolom MeSH
• mořská voda chemie   MeSH
• organické látky MeSH
• tandemová hmotnostní spektrometrie * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• organické látky MeSH

Realization of topological quantum states in carbon nanostructures has recently emerged as a promising platform for hosting highly coherent and controllable quantum dot spin qubits. However, their adjustable manipulation remains elusive. Here, we report the atomically accurate control of the hybridization level of topologically protected quantum edge states emerging from topological interfaces in bottom-up-fabricated π-conjugated polymers. Our investigation employed a combination of low-temperature scanning tunneling microscopy and spectroscopy, along with high-resolution atomic force microscopy, to effectively modify the hybridization level of neighboring edge states by the selective dehydrogenation reaction of molecular units in a pentacene-based polymer and demonstrate their reversible character. Density functional theory, tight binding, and complete active space calculations for the Hubbard model were employed to support our findings, revealing that the extent of orbital overlap between the topological edge states can be finely tuned based on the geometry and electronic bandgap of the interconnecting region. These results demonstrate the utility of topological edge states as components for designing complex quantum arrangements for advanced electronic devices.

• Klíčová slova
• atomic manipulation, noncontact atomic force microscopy, scanning tunneling microscopy, topological quantum phase transition, π-conjugated polymers,
• Publikační typ
• časopisecké články MeSH

This literature review provides a novel exploration of zinc's multifaceted roles in dermatology, with a particular focus on its potential integration into botulinum toxin formulations-an area that remains relatively underexplored in clinical practice. Zinc is widely recognized for its critical functions in skin health, including morphogenesis, regeneration, and protection, and its use in aesthetic medicine offers a unique opportunity for innovation. Specifically, incorporating zinc into botulinum toxin formulations could enhance the efficacy and stability of these treatments. Although zinc has historically been used in topical dermatological products and systemic health interventions, its potential in cosmetic preparations, such as anti-aging therapies or non-invasive aesthetic treatments, remains under-researched. Emerging patents suggest promising formulations combining zinc with botulinum toxin that may improve product stability and extend therapeutic effects. While current studies on oral zinc supplementation present mixed results concerning its ability to prolong botulinum toxin effects, this underscores the need for more rigorous investigation in the realm of aesthetic medicine. Zinc's well-established role in stabilizing dermatological products, such as sunscreens, and its applications in wound healing and skin regeneration, further highlights its potential for broader therapeutic uses beyond cosmetic applications. This review identifies a critical gap in the literature and calls for future research to optimize zinc concentrations and delivery methods specifically for aesthetic medical procedures, offering new insights into improving dermatological treatments beyond the scope of traditional cosmetic preparations.

• Klíčová slova
• aesthetic injectables, botulinum toxin, cosmetic science, dermatology, formulation stability, zinc,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Translational regulation is pivotal during preimplantation development. However, how mRNAs are selected for temporal regulation and their dynamic utilization and fate during this period are still unknown. Using a high-resolution ribosome profiling approach, we analyzed the transcriptome, as well as monosome- and polysome-bound RNAs of mouse oocytes and embryos, defining an unprecedented extent of spatiotemporal translational landscapes during this rapid developmental phase. We observed previously unknown mechanisms of translational selectivity, i.e., stage-wise deferral of loading monosome-bound mRNAs to polysome for active translation, continuous translation of both monosome and polysome-bound mRNAs at the same developmental stage, and priming to monosomes after initial activation. We showed that a eukaryotic initiation factor Eif1ad3, which is exclusively translated in the 2-Cell embryo, is required for ribosome biogenesis post embryonic genome activation. Our study thus provides genome-wide datasets and analyses of spatiotemporal translational dynamics accompanying mammalian germ cell and embryonic development and reveals the contribution of a novel translation initiation factor to mammalian pre-implantation development.

• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

In recent years, plastic and metal 3D printing has experienced massive development in the professional and hobby spheres, especially for rapid prototyping, reverse engineering, maintenance and quick repairs. However, this technology is limited by a number of factors, with the most common being the cost and availability of the technology but also the lack of information on material properties. This study focuses on investigating the material properties of PLA, PETG, HIPS, PA, ABS and ASA in order to elucidate their behavior in terms of wear and thermal resistance. The research builds on previous studies focusing on the mechanical properties of these materials and includes wear testing and DMA analysis. Weight loss, frictional forces, and frictional work including relative frictional work are recorded as part of this testing. The storage modulus and loss modulus including tan(δ) were then measured using DMA.

• Klíčová slova
• DMA, FDM, coefficient of friction, glass transition temperature, loss modulus, storage modulus, weight loss,
• Publikační typ
• časopisecké články MeSH

A newly identified subtype of hereditary axonal motor neuropathy, characterized by early proximal limb involvement, has been discovered in a cohort of 34 individuals with biallelic variants in von Willebrand factor A domain-containing 1 (VWA1). This study further delineates the disease characteristics in a cohort of 20 individuals diagnosed through genome or exome sequencing, incorporating neurophysiological, laboratory and imaging data, along with data from previously reported cases across three different studies. Newly reported clinical features include hypermobility/hyperlaxity, axial weakness, dysmorphic signs, asymmetric presentation, dystonic features and, notably, upper motor neuron signs. Foot drop, foot deformities and distal leg weakness followed by early proximal leg weakness are confirmed to be initial manifestations. Additionally, this study identified 11 novel VWA1 variants, reaffirming the 10 bp insertion-induced p.Gly25ArgfsTer74 as the most prevalent disease-causing allele, with a carrier frequency of ∼1 in 441 in the UK and Western European population. Importantly, VWA1-related pathology may mimic various neuromuscular conditions, advocating for its inclusion in diverse gene panels spanning hereditary neuropathies to muscular dystrophies. The study highlights the potential of lower quality control filters in exome analysis to enhance diagnostic yield of VWA1 disease that may account for up to 1% of unexplained hereditary neuropathies.

• Klíčová slova
• VWA1, neuromuscular disorders, neuromyopathy, recessive disorders,
• Publikační typ
• časopisecké články MeSH