Structural neuroplasticity such as neurite extension and dendritic spine dynamics is enhanced by brain-derived neurotrophic factor (BDNF) and impaired by types of inhibitory molecules that induce growth cone collapse and actin depolymerization, for example, myelin-associated inhibitors, chondroitin sulfate proteoglycans, and negative guidance molecules. These inhibitory molecules can activate RhoA/rho-associated coiled-coil containing protein kinase (ROCK) signaling (known to restrict structural plasticity). Intermittent hypoxia (IH) and high-intensity interval training (HIIT) are known to upregulate BDNF that is associated with improvements in learning and memory and greater functional recovery following neural insults. We investigated whether the RhoA/ROCK signaling pathway is also modulated by IH and HIIT in the hippocampus, cortex, and lumbar spinal cord of male Wistar rats. The gene expression of 25 RhoA/ROCK signaling pathway components was determined following IH, HIIT, or IH combined with HIIT (30 min/day, 5 days/wk, 6 wk). IH included 10 3-min bouts that alternated between hypoxia (15% O2) and normoxia. HIIT included 10 3-min bouts alternating between treadmill speeds of 50 cm·s-1 and 15 cm·s-1. In the hippocampus, IH and HIIT significantly downregulated Acan and NgR2 mRNA that are involved in the inhibition of neuroplasticity. However, IH and IH + HIIT significantly upregulated Lingo-1 and NgR3 in the cortex. This is the first time IH and HIIT have been linked to the modulation of plasticity-inhibiting pathways. These results provide a fundamental step toward elucidating the interplay between the neurotrophic and inhibitory mechanisms involved in experience-driven neural plasticity that will aid in optimizing physiological interventions for the treatment of cognitive decline or neurorehabilitation.NEW & NOTEWORTHY Intermittent hypoxia (IH) and high-intensity interval training (HIIT) enhance neuroplasticity and upregulate neurotrophic factors in the central nervous system (CNS). We provide evidence that IH and IH + HIIT also have the capacity to regulate genes involved in the RhoA/ROCK signaling pathway that is known to restrict structural plasticity in the CNS. This provides a new mechanistic insight into how these interventions may enhance hippocampal-related plasticity and facilitate learning, memory, and neuroregeneration.

• MeSH
• hipokampus * metabolismus   MeSH
• hypoxie metabolismus   patofyziologie   MeSH
• kinázy asociované s rho * metabolismus   genetika   MeSH
• krysa rodu rattus MeSH
• mícha metabolismus   fyziologie   MeSH
• mozková kůra metabolismus   fyziologie   MeSH
• neuroplasticita fyziologie   MeSH
• potkani Wistar * MeSH
• rho proteiny vázající GTP MeSH
• rhoA protein vázající GTP metabolismus   MeSH
• signální transdukce * fyziologie   MeSH
• vysoce intenzivní intervalový trénink * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Hyaluronan, a linear glycosaminoglycan comprising D-N-acetylglucosamine and D-glucuronic acid, is the main component of the extracellular matrix. Its influence on cell proliferation, migration, inflammation, signalling, and other functions, depends heavily on its molecular weight and chemical modification. Unsaturated HA oligosaccharides are available in defined length and purity. Their potential therapeutic utility can be further improved by chemical modification, e. g., reduction. No synthesis of such modified oligosaccharides, either stepwise or by hyaluronan cleavage, has been reported yet. Here we show a three-step synthesis (esterification, depolymerization and reduction) of unsaturated even numbered hyaluronan oligosaccharides with carboxylates and the reducing terminus reduced to an alcohol. Particular oligosaccharides were synthesised. The modified oligosaccharides are not cleaved by mammalian or bacterial hyaluronidase and do not affect the growth of mouse and human fibroblasts. Further, MTT and NRU viability tests showed that they inhibit the growth of human colon carcinoma cells HT-29 by 20-50 % in concentrations 500-1000 μg/mL. Interestingly, this effect takes place regardless of CD44 receptor expression and was not observed with unmodified HA oligosaccharides. These compounds could serve as enzymatically stable building blocks for biologically active substances.

• MeSH
• antigeny CD44 metabolismus   MeSH
• buňky HT-29 MeSH
• cytostatické látky * farmakologie   chemie   chemická syntéza   MeSH
• fibroblasty účinky léků   MeSH
• hyaluronoglukosaminidasa * metabolismus   antagonisté a inhibitory   MeSH
• kyselina hyaluronová * chemie   farmakologie   MeSH
• lidé MeSH
• myši MeSH
• oligosacharidy * chemie   farmakologie   MeSH
• proliferace buněk * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Atomic characterization of large nonfibrillar aggregates of amyloid polypeptides cannot be determined by experimental means. Starting from β-rich aggregates of Y and elongated topologies predicted by coarse-grained simulations and consisting of more than 100 Aβ16-22 peptides, we performed atomistic molecular dynamics (MD), replica exchange with solute scaling (REST2), and umbrella sampling simulations using the CHARMM36m force field in explicit solvent. Here, we explored the dynamics within 3 μs, the free energy landscape, and the potential of mean force associated with either the unbinding of one single peptide in different configurations within the aggregate or fragmentation events of a large number of peptides. Within the time scale of MD and REST2, we find that the aggregates experience slow global conformational plasticity, and remain essentially random coil though we observe slow beta-strand structuring with a dominance of antiparallel beta-sheets over parallel beta-sheets. Enhanced REST2 simulation is able to capture fragmentation events, and the free energy of fragmentation of a large block of peptides is found to be similar to the free energy associated with fibril depolymerization by one chain for longer Aβ sequences.

• MeSH
• amyloid chemie   MeSH
• amyloidní beta-protein * chemie   MeSH
• konformace proteinů, beta-řetězec MeSH
• peptidové fragmenty chemie   MeSH
• rozpouštědla chemie   MeSH
• simulace molekulární dynamiky * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Lignins are the most abundant biopolymers that consist of aromatic units. Lignins are obtained by fractionation of lignocellulose in the form of "technical lignins". The depolymerization (conversion) of lignin and the treatment of depolymerized lignin are challenging processes due to the complexity and resistance of lignins. Progress toward mild work-up of lignins has been discussed in numerous reviews. The next step in the valorization of lignin is the conversion of lignin-based monomers, which are limited in number, into a wider range of bulk and fine chemicals. These reactions may need chemicals, catalysts, solvents, or energy from fossil resources. This is counterintuitive to green, sustainable chemistry. Therefore, in this review, we focus on biocatalyzed reactions of lignin monomers, e.g., vanillin, vanillic acid, syringaldehyde, guaiacols, (iso)eugenol, ferulic acid, p-coumaric acid, and alkylphenols. For each monomer, its production from lignin or lignocellulose is summarized, and, mainly, its biotransformations that provide useful chemicals are discussed. The technological maturity of these processes is characterized based on, e.g., scale, volumetric productivities, or isolated yields. The biocatalyzed reactions are compared with their chemically catalyzed counterparts if the latter are available.

• MeSH
• fenoly * chemie   MeSH
• katalýza MeSH
• lignin * chemie   MeSH
• rozpouštědla chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The objective of the study was to investigate alkali lignin polymerization/depolymerization pathways in subcritical water (SW) without additives. Following a SW treatment at 200, 250, 275 and 300 °C, the products were subjected to a comprehensive suite of analyses addressing the product speciation and molecular weight (MW) distribution. The MW reduction (1.4 times) in the solid products following the SW treatment indicated a surprisingly reduced impact of cross-linking/repolymerization at 300 °C and lower temperatures. This was further confirmed by thermal carbon analysis (TCA) showing a reduction in pyrolytic charring after the SW treatment. The TD-Py gas chromatography analysis of the SW treated lignin indicated that the solid residue is less oxygenated than the initial lignin (23 vs. 29% as confirmed by elemental analysis). Thus, deoxygenation rather than re-polymerization appears to be the main process route in the absence of catalysts within the temperature range considered.

• MeSH
• lignin * MeSH
• polymerizace MeSH
• pyrolýza MeSH
• teplota MeSH
• voda * MeSH
• Publikační typ
• časopisecké články MeSH

The bacterium Pseudomonas putida KT2440 is gaining considerable interest as a microbial platform for biotechnological valorization of polymeric organic materials, such as lignocellulosic residues or plastics. However, P. putida on its own cannot make much use of such complex substrates, mainly because it lacks an efficient extracellular depolymerizing apparatus. We seek to address this limitation by adopting a recombinant cellulosome strategy for this host. In this work, we report an essential step in this endeavor-a display of designer enzyme-anchoring protein "scaffoldins", encompassing cohesin binding domains from divergent cellulolytic bacterial species on the P. putida surface. Two P. putida chassis strains, EM42 and EM371, with streamlined genomes and differences in the composition of the outer membrane were employed in this study. Scaffoldin variants were optimally delivered to their surface with one of four tested autotransporter systems (Ag43 from Escherichia coli), and the efficient display was confirmed by extracellular attachment of chimeric β-glucosidase and fluorescent proteins. Our results not only highlight the value of cell surface engineering for presentation of recombinant proteins on the envelope of Gram-negative bacteria but also pave the way toward designer cellulosome strategies tailored for P. putida.

• MeSH
• beta-glukosidasa metabolismus   MeSH
• celulosa metabolismus   MeSH
• celulozómy metabolismus   MeSH
• chromozomální proteiny, nehistonové chemie   MeSH
• Escherichia coli metabolismus   MeSH
• genom bakteriální * MeSH
• membránové proteiny metabolismus   MeSH
• metabolické inženýrství metody   MeSH
• proteinové domény MeSH
• proteiny buněčného cyklu chemie   MeSH
• proteiny z Escherichia coli metabolismus   MeSH
• Pseudomonas putida genetika   metabolismus   MeSH
• rekombinantní proteiny metabolismus   MeSH
• vnější bakteriální membrána metabolismus   MeSH
• zelené fluorescenční proteiny metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The aim of this paper is to review chromatographic and mass-spectrometric methods and underline the best analytical approaches for successful analysis of various hyaluronic acid species in different types of samples. Hyaluronan-degrading enzymes and chemical depolymerization produce di- or oligosaccharides suitable for hyaluronan quantification or structural characterization of hyaluronan derivatives. Efficient purification and pre-column derivatization of hyaluronan disaccharides by reductive amination allow subnanogram quantification in biological samples. The chromatographic separation is capable to distinguish all glycosaminoglycans disaccharides and to resolve hyaluronan fragments with 2-40 monomers. Using electrospray ionization or matrix assisted laser desorption ionization, hyaluronan fragments up to 8 kDa or 41 kDa, respectively, can be observed. One- or two-dimensional chromatographic separation with higly sensitive mass-spectrometric detection is an indispensable tool for revealing substituent position, extent of modification and substitution patterns of chemically modified hyaluronan derivatives. It is essential for studying structure-biological function relationships of hyaluronan and its derivatives.

• MeSH
• aminace MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací metody   MeSH
• kyselina hyaluronová analýza   chemie   MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice metody   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Fungi can improve stover digestibility due to their ability to secrete oxidative enzymes that depolymerize lignin, allowing the rumen microorganisms to access the polysaccharides of the plant cell wall. Some ascomycetes have shown good delignification capability; however, they have been scarcely evaluated for their ability to improve corn stover (CS) ruminal digestibility. We evaluated the laccase induction by CS of the CMU-196 strain of the ascomycete fungus Didymosphaeria sp. (syn. = Paraconiothyrium sp.). Also, we analyzed the capacity of such strain to modify the cell wall of CS and to improve its digestion by the ruminal microbiota. The CMU-196 strain showed a maximum extracellular laccase activity of 39.74 ± 0.24 U/L when an aqueous stover extract (SE, 10% v/v) was added to the growth medium. The addition of ground stover (GS, 2% w/v) increased the activity to a maximum of 262.27 ± 0.58 U/L. In solid-state fermentation (SSF) assays of GS, the strain degrades cell walls, destabilizing the vessels and tracheids of plant biomass; the protein content reaches a maximum of 33.2 g/kg dry matter (DM) at 70 days, while the crude fiber content shows the highest level of 314 g/kg DM at 14 days. SSF treatment of the CS increased the in vitro ruminal production of gas in a fraction that was considered nondigestible at 18 h, and gas production increased by 14% with respect to the untreated GS at 14 days. The CMU-196 strain can digest the plant cell wall and improve ruminal CS digestibility at a level equivalent to several basidiomycete species.

• MeSH
• Ascomycota enzymologie   růst a vývoj   metabolismus   MeSH
• bachor mikrobiologie   MeSH
• biomasa MeSH
• buněčná stěna metabolismus   ultrastruktura   MeSH
• fermentace MeSH
• krmivo pro zvířata analýza   mikrobiologie   MeSH
• kukuřice setá metabolismus   ultrastruktura   MeSH
• lakasa metabolismus   MeSH
• lignin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The integrity of the actin cytoskeleton is essential for plant immune signalling. Consequently, it is generally assumed that actin disruption reduces plant resistance to pathogen attack. Here, we demonstrate that actin depolymerization induced a dramatic increase in salicylic acid (SA) levels in Arabidopsis thaliana. Transcriptomic analysis showed that the SA pathway was activated due to the action of isochorismate synthase (ICS). The effect was also confirmed in Brassica napus. This raises the question of whether actin depolymerization could, under particular conditions, lead to increased resistance to pathogens. Thus, we explored the effect of pretreatment with actin-depolymerizing drugs on the resistance of Arabidopsis thaliana to the bacterial pathogen Pseudomonas syringae, and on the resistance of an important crop Brassica napus to its natural fungal pathogen Leptosphaeria maculans. In both pathosystems, actin depolymerization activated the SA pathway, leading to increased plant resistance. To our best knowledge, we herein provide the first direct evidence that disruption of the actin cytoskeleton can actually lead to increased plant resistance to pathogens, and that SA is crucial to this process.

• MeSH
• aktiny metabolismus   MeSH
• Arabidopsis metabolismus   mikrobiologie   MeSH
• Ascomycota patogenita   MeSH
• Brassica napus metabolismus   mikrobiologie   MeSH
• intramolekulární transferasy metabolismus   MeSH
• kyselina salicylová metabolismus   MeSH
• nemoci rostlin mikrobiologie   MeSH
• proteiny huseníčku metabolismus   MeSH
• Pseudomonas syringae patogenita   MeSH
• regulace genové exprese u rostlin fyziologie   MeSH
• signální transdukce fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Vinorelbin je semisyntetický vinca alkaloid druhé generace, který má nízkou afinitu k neurotubulům, z čehož vyplývá jeho nižší neurotoxicita. Vinca alkaloidy jsou mitotické jedy, které znemožňují správné vytváření mikrotubulů vazbou na tubulin. Způsobují tak depolymerizaci mikrotubulů a rozpouštění mitotického vřeténka, čímž zablokují dělení buněk a zapříčiňují poškození dalších dějů v závislosti na správné funkci mikrotubulů. V onkologii má vinorelbin širší využití, zejména v léčbě u metastazujícího karcinomu prsu a u nemalobuněčného plicního karcinomu, kde je použitelný ve všech stadiích v neoadjuvantní, adjuvantní i paliativní léčbě.

Vinorelbine is a second generation semisynthetic vinca alkaloid that has a low affinity for neurotubules, resulting in lower neurotoxicity. Vinca alkaloids are mitotic poisons that prevent the proper formation of microtubules by binding to tubulin. They cause depolymerization of microtubules and dissolution of the mitotic spindle, thereby blocking cell division and causing damage to other processes depending on the proper functioning of the microtubules. In oncology vinorelbine has a wider use, especially in metastatic breast cancer and non-small cell lung cancer, where it is applicable at all stages of non-adjuvant and palliative treatment.

• MeSH
• dospělí MeSH
• fatální výsledek MeSH
• fytogenní protinádorové látky terapeutické užití   MeSH
• indukce remise MeSH
• lidé MeSH
• mladý dospělý MeSH
• modulátory tubulinu terapeutické užití   MeSH
• nemalobuněčný karcinom plic * diagnóza   terapie   MeSH
• progrese nemoci MeSH
• vinorelbin * škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH