BACKGROUND: One of the main challenges in modern science is the amount of data produced by the experimental work; it is difficult to store, organize and share the scientific data and to extract the wealth of knowledge. Experimental method descriptions in scientific publications are often incomplete, which complicates experimental reproducibility. The proposed system was created in order to address these issues. It provides a solution for management of the experimental data and metadata to support the reproducibility. IMPLEMENTATION: The system is implemented as a repository for experiment descriptions and experimental data. It has three main entry points: desktop application for protocol design and data processing, web interface dedicated for protocol and data management, and web-based interface for mobile devices suitable for the field experiments. The functionality of desktop client can be extended using the custom plug-ins for data extraction and data processing. The system provides several methods to support experimental reproducibility: standardized terminology support, data and metadata at a single location, standardized protocol design or protocol evolution. RESULTS AND DISCUSSION: The system was tested in the framework of international infrastructure project AQUAEXCEL with five pilot installations at different institutes. The general testing in Tissue culture certified laboratory, Institute of complex systems and IFREMER verified the usability under different research infrastructures. The specific testing focused on the data processing modules and plug-ins demonstrated the modularity of the system for the specific conditions. The BioWes system represents experimental data as black box and therefore can handle any data type so as to provide broad usability for a variety of experiments and provide the data management infrastructure to improve the reproducibility and data sharing. CONCLUSIONS: The proposed system provides the tools for standard data management operations and extends the support by the standardization possibilities, protocol evolution with visualization features and modularity based on the data processing modules and device communication plug-ins. The software can be used at different organization levels: from a single researcher (to improve data organization) to research consortium through the central protocols management repository. Support from the protocol design until being shared with the standardization features helps to improve the reproducibility of research work. The platform provides support from experimental protocol design to cooperation using simple sharing.

• MeSH
• Internet * MeSH
• Cell Phone MeSH
• Reference Standards MeSH
• Software * MeSH
• Information Storage and Retrieval standards   MeSH
• User-Computer Interface MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Cell Biology MeSH
• Molecular Biology MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Biochemie. Molekulární biologie. Biofyzika
• NML Fields
• biologie
• cytologie, klinická cytologie

Toxoplasma gondii possesses sets of dense granule proteins (GRAs) that either assemble at, or cross the parasitophorous vacuole membrane (PVM) and exhibit motifs resembling the HT/PEXEL previously identified in a repertoire of exported Plasmodium proteins. Within Plasmodium spp., cleavage of the HT/PEXEL motif by the endoplasmic reticulum-resident protease Plasmepsin V precedes trafficking to and export across the PVM of proteins involved in pathogenicity and host cell remodelling. Here, we have functionally characterized the T. gondii aspartyl protease 5 (ASP5), a Golgi-resident protease that is phylogenetically related to Plasmepsin V. We show that deletion of ASP5 causes a significant loss in parasite fitness in vitro and an altered virulence in vivo. Furthermore, we reveal that ASP5 is necessary for the cleavage of GRA16, GRA19 and GRA20 at the PEXEL-like motif. In the absence of ASP5, the intravacuolar nanotubular network disappears and several GRAs fail to localize to the PVM, while GRA16 and GRA24, both known to be targeted to the host cell nucleus, are retained within the vacuolar space. Additionally, hypermigration of dendritic cells and bradyzoite cyst wall formation are impaired, critically impacting on parasite dissemination and persistence. Overall, the absence of ASP5 dramatically compromises the parasite's ability to modulate host signalling pathways and immune responses.

• MeSH
• Aspartic Acid Proteases metabolism   MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Fluorescent Antibody Technique MeSH
• Gene Knockout Techniques MeSH
• Golgi Apparatus enzymology   MeSH
• Host-Parasite Interactions physiology   MeSH
• Cells, Cultured MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Humans MeSH
• Molecular Sequence Data MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Toxoplasma enzymology   pathogenicity   MeSH
• Toxoplasmosis enzymology   MeSH
• Transfection MeSH
• Microscopy, Electron, Transmission MeSH
• Protein Transport MeSH
• Blotting, Western MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: The advancement of nanotechnology underscores the imperative need for establishing in silico predictive models to assess safety, particularly in the context of chronic respiratory afflictions such as lung fibrosis, a pathogenic transformation that is irreversible. While the compilation of predictive descriptors is pivotal for in silico model development, key features specifically tailored for predicting lung fibrosis remain elusive. This study aimed to uncover the essential predictive descriptors governing nanoparticle-induced pulmonary fibrosis. METHODS: We conducted a comprehensive analysis of the trajectory of metal oxide nanoparticles (MeONPs) within pulmonary systems. Two biological media (simulated lung fluid and phagolysosomal simulated fluid) and two cell lines (macrophages and epithelial cells) were meticulously chosen to scrutinize MeONP behaviors. Their interactions with MeONPs, also referred to as nano-bio interactions, can lead to alterations in the properties of the MeONPs as well as specific cellular responses. Physicochemical properties of MeONPs were assessed in biological media. The impact of MeONPs on cell membranes, lysosomes, mitochondria, and cytoplasmic components was evaluated using fluorescent probes, colorimetric enzyme substrates, and ELISA. The fibrogenic potential of MeONPs in mouse lungs was assessed by examining collagen deposition and growth factor release. Random forest classification was employed for analyzing in chemico, in vitro and in vivo data to identify predictive descriptors. RESULTS: The nano-bio interactions induced diverse changes in the 4 characteristics of MeONPs and had variable effects on the 14 cellular functions, which were quantitatively evaluated in chemico and in vitro. Among these 18 quantitative features, seven features were found to play key roles in predicting the pro-fibrogenic potential of MeONPs. Notably, IL-1β was identified as the most important feature, contributing 27.8% to the model's prediction. Mitochondrial activity (specifically NADH levels) in macrophages followed closely with a contribution of 17.6%. The remaining five key features include TGF-β1 release and NADH levels in epithelial cells, dissolution in lysosomal simulated fluids, zeta potential, and the hydrodynamic size of MeONPs. CONCLUSIONS: The pro-fibrogenic potential of MeONPs can be predicted by combination of key features at nano-bio interfaces, simulating their behavior and interactions within the lung environment. Among the 18 quantitative features, a combination of seven in chemico and in vitro descriptors could be leveraged to predict lung fibrosis in animals. Our findings offer crucial insights for developing in silico predictive models for nano-induced pulmonary fibrosis.

• MeSH
• A549 Cells MeSH
• Metal Nanoparticles * toxicity   chemistry   MeSH
• Humans MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Lung drug effects   pathology   metabolism   MeSH
• Pulmonary Fibrosis * chemically induced   metabolism   pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Neuronal Plasticity MeSH
• Trauma, Nervous System rehabilitation   MeSH
• Nerve Regeneration MeSH
• Rehabilitation MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• neurologie
• traumatologie
• neurochirurgie

• MeSH
• Neoplasms radiotherapy   MeSH
• Nuclear Medicine methods   MeSH
• Radiotherapy methods   MeSH
• Publication type
• Textbook MeSH

• Conspectus
• Učební osnovy. Vyučovací předměty. Učebnice
• Lékařské vědy. Lékařství
• NML Fields
• radiologie, nukleární medicína a zobrazovací metody
• onkologie
• NML Publication type
• kolektivní monografie

The aim of this study was to develop the potential tissue engineering applications of d-glucosamine (GlcN) immobilized onto the surface of a biodegradable matrix in order to induce a desired biological effect at biointerfaces. Thus, for sample preparation we used a novel multistep physicochemical approach. In the first step the poly(lactic acid) (PLA) films were exposed to a low pressure plasma in air atmosphere, followed by radical graft copolymerization with acrylic acid to yield a carboxyl-functionalized spacer layer on the PLA surface. The carboxyl groups were then coupled to GlcN molecules via the carbodiimide chemistry. The developed surfaces were characterized by X-ray Photoelectron Spectroscopy (XPS), Contact angle measurements and Atomic Force Microscopy (AFM). A preliminary study on the proliferation of fibroblasts on the developed surfaces was performed using the NIH/3T3 cell line.

• MeSH
• Biocompatible Materials chemistry   MeSH
• Photoelectron Spectroscopy MeSH
• Glucosamine chemistry   MeSH
• Microscopy, Atomic Force MeSH
• Polyesters chemistry   MeSH
• Surface Properties MeSH
• Cell Proliferation MeSH
• Regeneration * MeSH
• Wettability MeSH
• Tissue Engineering * MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Cell Biology MeSH
• Cell Cycle MeSH
• Cells MeSH
• DNA MeSH
• Genetic Code MeSH
• Genome MeSH
• Molecular Biology MeSH

• Conspectus
• Biochemie. Molekulární biologie. Biofyzika
• NML Fields
• biologie

Lens epithelium-derived growth factor/p75 (LEDGF/p75, or PSIP1) is a transcriptional coactivator that tethers other proteins to gene bodies. The chromatin tethering function of LEDGF/p75 is hijacked by HIV integrase to ensure viral integration at sites of active transcription. LEDGF/p75 is also important for the development of mixed-lineage leukemia (MLL), where it tethers the MLL1 fusion complex at aberrant MLL targets, inducing malignant transformation. However, little is known about how the LEDGF/p75 protein interaction network is regulated. Here, we obtained solution structures of the complete interfaces between the LEDGF/p75 integrase binding domain (IBD) and its cellular binding partners and validated another binding partner, Mediator subunit 1 (MED1). We reveal that structurally conserved IBD-binding motifs (IBMs) on known LEDGF/p75 binding partners can be regulated by phosphorylation, permitting switching between low- and high-affinity states. Finally, we show that elimination of IBM phosphorylation sites on MLL1 disrupts the oncogenic potential of primary MLL1-rearranged leukemic cells. Our results demonstrate that kinase-dependent phosphorylation of MLL1 represents a previously unknown oncogenic dependency that may be harnessed in the treatment of MLL-rearranged leukemia.

• MeSH
• Adaptor Proteins, Signal Transducing genetics   metabolism   MeSH
• Amino Acid Motifs MeSH
• Phosphorylation genetics   MeSH
• Histone-Lysine N-Methyltransferase genetics   metabolism   MeSH
• HIV Integrase genetics   metabolism   MeSH
• HIV enzymology   genetics   MeSH
• Humans MeSH
• Mediator Complex Subunit 1 genetics   metabolism   MeSH
• Cell Line, Tumor MeSH
• Myeloid-Lymphoid Leukemia Protein genetics   metabolism   MeSH
• Transcription Factors genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Ticks are hematophagous arachnids transmitting a wide variety of pathogens including viruses, bacteria, and protozoans to their vertebrate hosts. The tick vector competence has to be intimately linked to the ability of transmitted pathogens to evade tick defense mechanisms encountered on their route through the tick body comprising midgut, hemolymph, salivary glands or ovaries. Tick innate immunity is, like in other invertebrates, based on an orchestrated action of humoral and cellular immune responses. The direct antimicrobial defense in ticks is accomplished by a variety of small molecules such as defensins, lysozymes or by tick-specific antimicrobial compounds such as microplusin/hebraein or 5.3-kDa family proteins. Phagocytosis of the invading microbes by tick hemocytes is likely mediated by the primordial complement-like system composed of thioester-containing proteins, fibrinogen-related lectins and convertase-like factors. Moreover, an important role in survival of the ingested microbes seems to be played by host proteins and redox balance maintenance in the tick midgut. Here, we summarize recent knowledge about the major components of tick immune system and focus on their interaction with the relevant tick-transmitted pathogens, represented by spirochetes (Borrelia), rickettsiae (Anaplasma), and protozoans (Babesia). Availability of the tick genomic database and feasibility of functional genomics based on RNA interference greatly contribute to the understanding of molecular and cellular interplay at the tick-pathogen interface and may provide new targets for blocking the transmission of tick pathogens.

• MeSH
• Anaplasma immunology   pathogenicity   MeSH
• Arachnid Vectors immunology   microbiology   parasitology   MeSH
• Babesia immunology   pathogenicity   MeSH
• Borrelia immunology   pathogenicity   MeSH
• Host-Pathogen Interactions * MeSH
• Ticks immunology   microbiology   parasitology   MeSH
• Immunity, Innate * MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH