Redox signaling from mitochondria (mt) to the cytosol and plasma membrane (PM) has been scarcely reported, such as in the case of hypoxic cell adaptation or (2-oxo-) 2-keto-isocaproate (KIC) β-like-oxidation stimulating insulin secretion in pancreatic β-cells. Mutual redox state influence between mitochondrial major compartments, the matrix and the intracristal space, and the cytosol is therefore derived theoretically in this article to predict possible conditions, when mt-to-cytosol and mt-to-PM signals may occur, as well as conditions in which the cytosolic redox signaling is not overwhelmed by the mitochondrial antioxidant capacity. Possible peroxiredoxin 3 participation in mt-to-cytosol redox signaling is discussed, as well as another specific case, whereby mitochondrial superoxide release is diminished, whereas the matrix MnSOD is activated. As a result, the enhanced conversion to H2O2 allows H2O2 diffusion into the cytosol, where it could be a predominant component of the H2O2 release. In both of these ways, mt-to-cytosol and mt-to-PM signals may be realized. Finally, the use of redox-sensitive probes is discussed, which disturb redox equilibria, and hence add a surplus redox-buffering to the compartment, where they are localized. Specifically, when attempts to quantify net H2O2 fluxes are to be made, this should be taken into account.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Significance: Mitochondrial (mt) reticulum network in the cell possesses amazing ultramorphology of parallel lamellar cristae, formed by the invaginated inner mitochondrial membrane. Its non-invaginated part, the inner boundary membrane (IBM) forms a cylindrical sandwich with the outer mitochondrial membrane (OMM). Crista membranes (CMs) meet IBM at crista junctions (CJs) of mt cristae organizing system (MICOS) complexes connected to OMM sorting and assembly machinery (SAM). Cristae dimensions, shape, and CJs have characteristic patterns for different metabolic regimes, physiological and pathological situations. Recent Advances: Cristae-shaping proteins were characterized, namely rows of ATP-synthase dimers forming the crista lamella edges, MICOS subunits, optic atrophy 1 (OPA1) isoforms and mitochondrial genome maintenance 1 (MGM1) filaments, prohibitins, and others. Detailed cristae ultramorphology changes were imaged by focused-ion beam/scanning electron microscopy. Dynamics of crista lamellae and mobile CJs were demonstrated by nanoscopy in living cells. With tBID-induced apoptosis a single entirely fused cristae reticulum was observed in a mitochondrial spheroid. Critical Issues: The mobility and composition of MICOS, OPA1, and ATP-synthase dimeric rows regulated by post-translational modifications might be exclusively responsible for cristae morphology changes, but ion fluxes across CM and resulting osmotic forces might be also involved. Inevitably, cristae ultramorphology should reflect also mitochondrial redox homeostasis, but details are unknown. Disordered cristae typically reflect higher superoxide formation. Future Directions: To link redox homeostasis to cristae ultramorphology and define markers, recent progress will help in uncovering mechanisms involved in proton-coupled electron transfer via the respiratory chain and in regulation of cristae architecture, leading to structural determination of superoxide formation sites and cristae ultramorphology changes in diseases. Antioxid. Redox Signal. 39, 635-683.
Significance: Mitochondria determine glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells by elevating ATP synthesis. As the metabolic and redox hub, mitochondria provide numerous links to the plasma membrane channels, insulin granule vesicles (IGVs), cell redox, NADH, NADPH, and Ca2+ homeostasis, all affecting insulin secretion. Recent Advances: Mitochondrial redox signaling was implicated in several modes of insulin secretion (branched-chain ketoacid [BCKA]-, fatty acid [FA]-stimulated). Mitochondrial Ca2+ influx was found to enhance GSIS, reflecting cytosolic Ca2+ oscillations induced by action potential spikes (intermittent opening of voltage-dependent Ca2+ and K+ channels) or the superimposed Ca2+ release from the endoplasmic reticulum (ER). The ATPase inhibitory factor 1 (IF1) was reported to tune the glucose sensitivity range for GSIS. Mitochondrial protein kinase A was implicated in preventing the IF1-mediated inhibition of the ATP synthase. Critical Issues: It is unknown how the redox signal spreads up to the plasma membrane and what its targets are, what the differences in metabolic, redox, NADH/NADPH, and Ca2+ signaling, and homeostasis are between the first and second GSIS phase, and whether mitochondria can replace ER in the amplification of IGV exocytosis. Future Directions: Metabolomics studies performed to distinguish between the mitochondrial matrix and cytosolic metabolites will elucidate further details. Identifying the targets of cell signaling into mitochondria and of mitochondrial retrograde metabolic and redox signals to the cell will uncover further molecular mechanisms for insulin secretion stimulated by glucose, BCKAs, and FAs, and the amplification of secretion by glucagon-like peptide (GLP-1) and metabotropic receptors. They will identify the distinction between the hub β-cells and their followers in intact and diabetic states. Antioxid. Redox Signal. 36, 920-952.
- MeSH
- adenosintrifosfát metabolismus MeSH
- beta-buňky * metabolismus MeSH
- glukosa metabolismus MeSH
- inzulin metabolismus MeSH
- Langerhansovy ostrůvky * metabolismus MeSH
- mitochondrie metabolismus MeSH
- NAD metabolismus MeSH
- NADP metabolismus MeSH
- sekrece inzulinu MeSH
- sekretagoga metabolismus MeSH
- vápník metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
V článku je popsán případ sepse u člověka pracujícího v zemědělství s fatálním vyústěním způsobený druhem Actinobacillus suis/ A. equuli. Článek je doplněn informacemi o identifikaci a výsledky vyšetření citlivosti k antibiotikům. Jde o ojedinělý případ humánní infekce a pravděpodobně o první případ infekce člověka v České republice způsobený tímto druhem.
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V článku je popsán případ vzácné yersiniové infekce vyvolané druhem Yersinia pseudotuberculosis u pětiletého chlapce přijatého k hospitalizaci. Infekce probíhala pod obrazem tzv. syndromu pravého dolního kvadrantu, resp. terminální ileitis. Kmen yersinie byl izolován ze stolice a jsou zde uvedeny jeho biochemické vlastnosti. Konfirmaci provedla Národní referenční laboratoř pro E. coli a shigely. Pseudotuberkulóza se v ČR vyskytuje velmi vzácně, a proto si autoři dovolují na tuto infekci upozornit. Zvětšení mízních uzlin v pravém dolním kvadrantu břicha by mělo vzbudit podezření na toto onemocnění.
The article describes a case of a rare infection caused by Yersinia pseudotuberculosis in a five-year-old boy admitted to the hospital. The infection was manifested by the so-called right lower quadrant syndrome, or terminal ileitis. The Y. pseudotuberculosis strain was isolated from the patient’s feces and its biochemical properties are reported. Confirmation was performed by the National Reference Laboratory for E. coli and Shigella. Since pseudotuberculosis is very rare in the Czech Republic, the authors would like to draw attention to this infection. Enlargement of lymph nodes in the right lower quadrant of the abdomen may suggest the infection caused by Y. pseudotuberculosis.
Pancreatic β-cell insulin secretion, which responds to various secretagogues and hormonal regulations, is reviewed here, emphasizing the fundamental redox signaling by NADPH oxidase 4- (NOX4-) mediated H2O2 production for glucose-stimulated insulin secretion (GSIS). There is a logical summation that integrates both metabolic plus redox homeostasis because the ATP-sensitive K+ channel (KATP) can only be closed when both ATP and H2O2 are elevated. Otherwise ATP would block KATP, while H2O2 would activate any of the redox-sensitive nonspecific calcium channels (NSCCs), such as TRPM2. Notably, a 100%-closed KATP ensemble is insufficient to reach the -50 mV threshold plasma membrane depolarization required for the activation of voltage-dependent Ca2+ channels. Open synergic NSCCs or Cl- channels have to act simultaneously to reach this threshold. The resulting intermittent cytosolic Ca2+-increases lead to the pulsatile exocytosis of insulin granule vesicles (IGVs). The incretin (e.g., GLP-1) amplification of GSIS stems from receptor signaling leading to activating the phosphorylation of TRPM channels and effects on other channels to intensify integral Ca2+-influx (fortified by endoplasmic reticulum Ca2+). ATP plus H2O2 are also required for branched-chain ketoacids (BCKAs); and partly for fatty acids (FAs) to secrete insulin, while BCKA or FA β-oxidation provide redox signaling from mitochondria, which proceeds by H2O2 diffusion or hypothetical SH relay via peroxiredoxin "redox kiss" to target proteins.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The Neurodata Without Borders (abbreviation NWB) format is a current technology for storing neurophysiology data along with the associated metadata. Data stored in the format is organized into separate HDF5 files, each file usually storing the data associated with a single recording session. While the NWB format provides a structured method for storing data, so far there have not been tools which enable searching a collection of NWB files in order to find data of interest for a particular purpose. We describe here three tools to enable searching NWB files. The tools have different features making each of them most useful for a particular task. The first tool, called the NWB Query Engine, is written in Java. It allows searching the complete content of NWB files. It was designed for the first version of NWB (NWB 1) and supports most (but not all) features of the most recent version (NWB 2). For some searches, it is the fastest tool. The second tool, called "search_nwb" is written in Python and also allow searching the complete contents of NWB files. It works with both NWB 1 and NWB 2, as does the third tool. The third tool, called "nwbindexer" enables searching a collection of NWB files using a two-step process. In the first step, a utility is run which creates an SQLite database containing the metadata in a collection of NWB files. This database is then searched in the second step, using another utility. Once the index is built, this two-step processes allows faster searches than are done by the other tools, but does not enable as complete of searches. All three tools use a simple query language which was developed for this project. Software integrating the three tools into a web-interface is provided which enables searching NWB files by submitting a web form.
- Publikační typ
- časopisecké články MeSH
Actinomyces urogenitalis je spojována nejčastěji s urogenitálním aparátem člověka a většinou pouze jako rezidentní flóra. V extra-urogenitálních lokalizacích je izolována jen velmi sporadicky. V článku jsou stručně popsány dvě kazuistiky extraurogenitálních infekcí člověka a zkušenosti s mikrobiologickou diagnostikou této aktinomycety. Vyšetření citlivosti k antibiotikům je zaměřeno zejména na rezistenci k linkosamidům a fluorochinolonům, včetně uvedení metody testování. V článku jsou také uvedeny dosud známé případy extraurogenitálních infekcí jinde ve světě. Publikace přispívá k rozšíření znalostí o výskytu, diagnostice a citlivosti k antibiotikům, především u dosud vzácně popisovaných extra-urogenitálních infekcí, vyvolaných tímto druhem aktinomycety. Přesná druhová diagnostika mikroorganismů je v rutinní laboratoři významná pro stanovení etiologického významu mikroorganismu a pro přesnější případné nastavení empirické antibiotické terapie.
Actinomyces urogenitalis is most commonly associated with the human genitourinary system, often only as the resident flora. Outside the genitourinary tract, A. urogenitalis is isolated rather sporadically. Presented are two brief case reports of human infections outside the genitourinary tract as well as experiences with microbiological identification of this actinomycete. Antibiotic susceptibility testing of actinomycetes is focused especially on their resistance to lincosamides and fluoroquinolones. The etiological relationship with the patients’ clinical problems was not investigated. Previously reported cases of infections outside the genitourinary tract are also mentioned in the article. The article may aid in expanding the knowledge of the occurrence, diagnosis and susceptibility of A. urogenitalis to antibiotics, par- ticularly in rarely reported extra-genitourinary infections caused by this species. Accurate species identification in routine laboratory practice is important both for determination of the etiological role of the microorganism and for more precise selection of empirical antibiotic therapy.
- Klíčová slova
- Actinomyces urogenitalis,
- MeSH
- Actinomycetaceae patogenita účinky léků MeSH
- aktinomykóza farmakoterapie terapie MeSH
- antibakteriální látky terapeutické užití MeSH
- antibiotická rezistence MeSH
- dospělí MeSH
- infekce bakteriemi řádu Actinomycetales * farmakoterapie terapie MeSH
- infekční nemoci kůže mikrobiologie terapie MeSH
- lidé MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Autoři uvádějí v článku kazuistiky tří případů bakterémie s izolací velmi vzácných mikroorganismů u hospitalizovaných pacientů. U jednotlivých případů je vždy uvedena stručná kazuistika s úvahou k možné etiologické souvislosti s diagnózou a ke klinickému stavu pacienta. Rutinní mikrobiologická diagnostika byla provedena vyšetřením biochemických vlastností komerčními soupravami. Přesné určení mikroorganismů do druhu bylo provedeno ve Státním zdravotním ústavu v Praze metodou hmotnostní spektrometrie MALDI-TOF MS a 16S rDNA sekvenací. Citlivost k antibiotikům byla vyšetřena diskovým difuzním testem a stanovením minimální inhibiční koncentrace mikrometodou ředění na mikrodestičce. V některých případech bylo doplněno vyšetřením metodou vzestupného gradientu (E testy). Izolace Stenotrophomonas acidaminiphila je pravděpodobně vůbec prvním případem záchytu z humánního klinického materiálu.
The authors present three case reports of bacteremia with very rare microorganisms being isolated in the patients. Each brief case report is accompanied by etiological considerations related to the diagnosis and clinical condition of the patient. Routine microbiology tests were performed by examining the biochemical properties using commercial kits. Two methods were used to determine the microorganism species in the State Institute of Public Health in Prague: MALDI-TOF MS and 16S rDNA sequencing. Antibiotic susceptibility was assessed by the disk diffusion test; minimum inhibitory concentrations were determined using broth microdilution and the gradient diffusion method (E tests). This is probably the first reported case of Stenotrophomonas acidaminiphila isolated from human clinical specimens.
