Monocercomonoides exilis is the first known amitochondriate eukaryote. Loss of mitochondria in M. exilis ocurred after the replacement of the essential mitochondrial iron-sulfur cluster (ISC) assembly machinery by a unique, bacteria-derived, cytosolic SUF system. It has been hypothesized that the MeSuf pathway, in cooperation with proteins of the cytosolic iron-sulfur protein assembly (CIA) system, is responsible for the biogenesis of FeS clusters in M. exilis, yet biochemical evidence is pending. Here, we address the M. exilis MeSuf system and show that SUF genes, individually or in tandem, support the loading of iron-sulfur (FeS) clusters into the reporter protein IscR in Escherichia coli. The Suf proteins MeSufB, MeSufC, and MeSufDSU interact in vivo with one another and with Suf proteins of E. coli. In vitro, the M. exilis Suf proteins form large complexes of varying composition and hence may function as a dynamic biosynthetic system in the protist. The putative FeS cluster scaffold MeSufB-MeSufC (MeSufBC) forms multiple oligomeric complexes, some of which bind FeS clusters and form selectively only in the presence of adenosine nucleotides. The multi-domain fusion protein MeSufDSU binds a PLP cofactor and can form higher-order complexes with MeSufB and MeSufC. Our work demonstrates the biochemical property of M. exilis Suf proteins to act as a functional FeS cluster assembly system and provides insights into the molecular mechanism of this unique eukaryotic SUF system.
- Klíčová slova
- FeS clusters, SUF system, amitochondriate, functional protistology, protist,
- MeSH
- Escherichia coli metabolismus genetika MeSH
- proteiny obsahující železo a síru * metabolismus genetika MeSH
- protozoální proteiny metabolismus genetika MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- proteiny obsahující železo a síru * MeSH
- protozoální proteiny MeSH
AIM: This study examines the combination of FES-PET and FDG-PET as complementary imaging for detection of metastatic ILC. METHODS: We retrospectively evaluated FES and FDG uptake in patients with metastatic ILC from an estrogen receptor (ER) positive primary tumor. We classified lesions into three categories (FES high/FDG low, FES high/FDG high, FES low/FDG low) using SUVmax cut-off values of 1.5 for FES and 5.0 for FDG. Qualitative evaluation included examination of the difference in the extent of disease between FES and FDG. RESULTS: Of the 38 patients, 82% had FES uptake in all tumor sites identified by FDG, with 18% lacking FES uptake in at least one lesion. Mean (range) SUVmax for FES and FDG was 4.0 (0.67-10.6) and 4.6 (1.3-12.5), respectively. The majority of ILC patients (25/38), had lesions with FES high/FDG low uptake, consistent with the strongly ER + indolent nature of ILC. Patients with disease classified as FES high/FDG low had longer median overall survival (OS) (3.2 years) and progression-free survival (PFS) (1.5 years) than FES high/FDG high (OS = 2.1 years and PFS = 0.46 years). The median overall OS for all patients was 3.0 years (95% CI 2.5, 4.8) and PFS of 1.3 years (95% CI 0.6, 2.5). 8 patients (21%) had qualitatively more extensive disease by FES-PET. CONCLUSIONS: Our findings suggest that both FES-PET and FDG-PET can identify metastatic ILC and be useful in detecting the pattern and extent of disease. The imaging combination provides additional information for prognosis and clinical decision making, balancing suitability for endocrine therapy and aggressiveness/indolence of disease.
- Klíčová slova
- FDG, FES, Lobular breast cancer,
- MeSH
- dospělí MeSH
- estradiol * analogy a deriváty chemie MeSH
- fluorodeoxyglukosa F18 * chemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lobulární karcinom * diagnostické zobrazování terapie patologie MeSH
- metastázy nádorů MeSH
- nádory prsu * diagnostické zobrazování patologie terapie MeSH
- pozitronová emisní tomografie * metody MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 16-fluoroestradiol MeSH Prohlížeč
- estradiol * MeSH
- fluorodeoxyglukosa F18 * MeSH
Zero-valent iron nanoparticles (nZVI) treated by reduced sulfur compounds (i.e., sulfidated nZVI, S-nZVI) have attracted increased attention as promising materials for environmental remediation. While the preparation of S-nZVI and its reactions with various groundwater contaminants such as trichloroethylene (TCE) were already a subject of several studies, nanoparticle synthesis procedures investigated so far were suited mainly for laboratory-scale preparation with only a limited possibility of easy and cost-effective large-scale production and FeS shell property control. This study presents a novel approach for synthesizing S-nZVI using commercially available nZVI particles that are treated with sodium sulfide in a concentrated slurry. This leads to S-nZVI particles that do not contain hazardous boron residues and can be easily prepared off-site. The resulting S-nZVI exhibits a core-shell structure where zero-valent iron is the dominant phase in the core, while the shell contains mostly amorphous iron sulfides. The average FeS shell thickness can be controlled by the applied sulfide concentration. Up to a 12-fold increase in the TCE removal and a 7-fold increase in the electron efficiency were observed upon amending nZVI with sulfide. Although the FeS shell thickness correlated with surface-area-normalized TCE removal rates, sulfidation negatively impacted the particle surface area, resulting in an optimal FeS shell thickness of approximately 7.3 nm. This corresponded to a particle S/Fe mass ratio of 0.0195. At all sulfide doses, the TCE degradation products were only fully dechlorinated hydrocarbons. Moreover, a nearly 100% chlorine balance was found at the end of the experiments, further confirming complete TCE degradation and the absence of chlorinated transformation products. The newly synthesized S-nZVI particles thus represent a promising remedial agent applicable at sites contaminated with TCE.
- Klíčová slova
- dechlorination, nanoparticles, selectivity, sulfidation, trichloroethylene, zero-valent iron,
- Publikační typ
- časopisecké články MeSH
A pulsed Nd : YAG laser ablation of FeS in water and ethanol produces FeS-derived colloidal nanoparticles that absorb onto immersed porous ceramic substrates and create solar-light photocatalytic surfaces. The stability, size distribution and zeta potential of the nanoparticles were assessed by dynamic light scattering. Raman, UV-Vis and XP spectroscopy and electron microscopy reveal that the sol nanoparticles have their outmost layer composed of ferrous and ferric sulphates and those produced in water are made of high-pressure orthorhombic FeS, cubic magnetite Fe3O4 and tetragonal maghemite γ-Fe2O3, while those formed in ethanol contain hexagonal FeS and cubic magnetite Fe3O4. Both colloids absorb solar light and their adsorption to porous ceramic surfaces creates functionalized ceramic surfaces that induce methylene blue degradation by daylight. The laser induced process thus offers an easy and efficient way for the functionalization of porous surfaces by photocatalytic nanoparticles that avoids aggregation in the liquid phase. The formation of an orthorhombic high-pressure FeS phase stable under ambient conditions is the first example of high-pressure structures produced by laser ablation in liquid without the assistance of an electric field.
- Publikační typ
- časopisecké články MeSH
Mitochondria are the site of assembly of FeS centers of mitochondrial and cytosolic FeS proteins. Various microaerophilic or anaerobic unicellular eukaryotes lack typical mitochondria ("amitochondriate" protists). In some of these organisms, a metabolically different organelle, the hydrogenosome, is found, which is thought to derive from the same proteobacterial ancestor as mitochondria. Here, we show that hydrogenosomes of Trichomonas vaginalis, a human genitourinary parasite, contain a key enzyme of FeS center biosynthesis, cysteine desulfurase (TviscS-2), which is phylogenetically related to its mitochondrial homologs. Hydrogenosomes catalyze the enzymatic assembly and insertion of FeS centers into apoproteins, as shown by the reconstruction of the apoform of [2Fe-2S]ferredoxin and the incorporation of 35S from labeled cysteine. Our results indicate that the biosynthesis of FeS proteins is performed by a homologous system in mitochondriate and amitochondriate eukaryotes and that this process is inherited from the proteobacterial ancestor of mitochondria.
- MeSH
- ferredoxiny genetika metabolismus MeSH
- genetická transkripce MeSH
- mitochondrie MeSH
- molekulární sekvence - údaje MeSH
- organely fyziologie MeSH
- protozoální proteiny genetika metabolismus MeSH
- Trichomonas vaginalis genetika ultrastruktura MeSH
- vodík metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- Názvy látek
- ferredoxiny MeSH
- protozoální proteiny MeSH
- vodík MeSH
N-methyl-D-aspartate receptors (NMDARs) are a subtype of ionotropic glutamate receptors critical for synaptic transmission and plasticity, and for the development of neural circuits. Rare or de-novo variants in GRIN genes encoding NMDAR subunits have been associated with neurodevelopmental disorders characterized by intellectual disability, developmental delay, autism, schizophrenia, or epilepsy. In recent years, some disease-associated variants in GRIN genes have been characterized using recombinant receptors expressed in non-neuronal cells, and a few variants have also been studied in neuronal preparations or animal models. Here we review the current literature on the functional evaluation of human disease-associated variants in GRIN1, GRIN2A and GRIN2B genes at all levels of analysis. Focusing on the impact of different patient variants at the level of receptor function, we discuss effects on receptor agonist and co-agonist affinity, channel open probability, and receptor cell surface expression. We consider how such receptor-level functional information may be used to classify variants as gain-of-function or loss-of-function, and discuss the limitations of this classification at the synaptic, cellular, or system level. Together this work by many laboratories worldwide yields valuable insights into NMDAR structure and function, and represents significant progress in the effort to understand and treat GRIN disorders. Keywords: NMDA receptor , GRIN genes, Genetic variants, Electrophysiology, Synapse, Animal models.
- MeSH
- genetická predispozice k nemoci MeSH
- genetická variace MeSH
- lidé MeSH
- neurovývojové poruchy genetika MeSH
- proteiny nervové tkáně genetika metabolismus MeSH
- receptory N-methyl-D-aspartátu * genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- GRIN1 protein, human MeSH Prohlížeč
- N-methyl D-aspartate receptor subtype 2A MeSH Prohlížeč
- NR2B NMDA receptor MeSH Prohlížeč
- proteiny nervové tkáně MeSH
- receptory N-methyl-D-aspartátu * MeSH
INTRODUCTION: The article is one of the very first autopsy reports worldwide, which associates COVID-19 infection and pulmonary fat embolism. AIMS: To point to a crucial connection between a severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) infection and pulmonary fat embolism as one of the possible major mechanisms of severe COVID-19 symptoms. METHODS: Lung, brain and kidney tissues examination of 16 full human autopsy cases. All deceased suffered from COVID-19 infection, none of them was admitted to hospital prior to death, immediate causes of death vary. Autopsies accompanied by microbiological examination and histological examination using Oil Red O staining were performed. Consequently, we have implemented a control cohort consisting of 16 deceased with no presence of pulmonary infection and various immediate causes of death. RESULTS: Of the 16 autopsy cases, 11 (68.8%) were males and 5 (31.3%) females, with overall mean age 68.1 (39-86) years. Causes of death of studied subjects were natural, mostly from respiratory failure (in 12 cases, 75%). Cardiopulmonary resuscitation was performed in 7 cases (43.8%). None of dissected persons had larger signs of body trauma. Pulmonary fat embolism was found in 11 cases (68.8%), which generalised to kidneys in 8 patients (50% of all cases, 72.3% of cases with pulmonary fat embolism) and to brain tissue in 1 case. CONCLUSION: We demonstrated a reasonable relation between a COVID-19 disease and a variously severe fat embolism, severity of which does not directly correlate with body weight. Further investigation or even change of medical treatment needs to be considered in patients with COVID-19.
- Klíčová slova
- COVID-19, FES, autopsy, coronavirus, fat embolism, post-mortem,
- Publikační typ
- časopisecké články MeSH
The importance of iron in the growth and progression of tumors has been widely documented. In this report, we show that tumor-initiating cells (TICs), represented by spheres derived from the MCF7 cell line, exhibit higher intracellular labile iron pool, mitochondrial iron accumulation and are more susceptible to iron chelation. TICs also show activation of the IRP/IRE system, leading to higher iron uptake and decrease in iron storage, suggesting that level of properly assembled cytosolic iron-sulfur clusters (FeS) is reduced. This finding is confirmed by lower enzymatic activity of aconitase and FeS cluster biogenesis enzymes, as well as lower levels of reduced glutathione, implying reduced FeS clusters synthesis/utilization in TICs. Importantly, we have identified specific gene signature related to iron metabolism consisting of genes regulating iron uptake, mitochondrial FeS cluster biogenesis and hypoxic response (ABCB10, ACO1, CYBRD1, EPAS1, GLRX5, HEPH, HFE, IREB2, QSOX1 and TFRC). Principal component analysis based on this signature is able to distinguish TICs from cancer cells in vitro and also Leukemia-initiating cells (LICs) from non-LICs in the mouse model of acute promyelocytic leukemia (APL). Majority of the described changes were also recapitulated in an alternative model represented by MCF7 cells resistant to tamoxifen (TAMR) that exhibit features of TICs. Our findings point to the critical importance of redox balance and iron metabolism-related genes and proteins in the context of cancer and TICs that could be potentially used for cancer diagnostics or therapy.
- Klíčová slova
- FeS cluster, breast cancer, iron metabolism, stem cells, tumor-initiating cells,
- MeSH
- akutní promyelocytární leukemie enzymologie genetika MeSH
- analýza hlavních komponent MeSH
- biologický transport MeSH
- buněčné sféroidy MeSH
- chelátory železa farmakologie MeSH
- chemorezistence MeSH
- fenotyp MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- mitochondrie enzymologie MeSH
- myši transgenní MeSH
- nádorové kmenové buňky účinky léků enzymologie patologie MeSH
- nádory prostaty farmakoterapie enzymologie genetika patologie MeSH
- nádory prsu farmakoterapie enzymologie genetika patologie MeSH
- protinádorové látky farmakologie MeSH
- regulace genové exprese enzymů MeSH
- regulace genové exprese u nádorů MeSH
- stanovení celkové genové exprese MeSH
- tamoxifen farmakologie MeSH
- transkriptom * MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chelátory železa MeSH
- protinádorové látky MeSH
- tamoxifen MeSH
- železo MeSH
Iron aluminides are still deeply investigated materials for their use in power plants, automotive and chemical industry, and other sectors. This paper shows that it is possible to strongly improve their oxidation behavior by the addition of silicon. The description of the synergic effect of aluminum and silicon on the oxidation behavior of Fe-Al-Si alloys at 800 °C in air is presented. The oxidation rate, microstructure, phase, and chemical composition of these ternary alloys are compared with the binary Fe-Al and Fe-Si alloys. Results showed that the oxidation of Fe-Al-Si ternary alloys provides an oxide layer based on aluminum oxide with a low concentration of iron and silicon. Below this oxide layer, there is a layer of silicides formed as a result of depletion by aluminum, which forms a secondary oxidation protection.
- Klíčová slova
- Fe–Al–Si alloy, iron aluminide, iron silicide, oxidation,
- Publikační typ
- časopisecké články MeSH
Identification of unstable high-valent iron species in electron transfer reactions of ferrate(VI) (Fe(VI)O4(2-), Fe(VI)) has been an important challenge in advancing the understanding of the oxidative mechanisms of ferrates. This paper presents the first example of distinguishing various phases differing in the valence state of iron in the solid state reduction of Fe(VI) to Fe(III) oxides at 235 °C using hyperfine parameters, isomer shift and hyperfine magnetic field, obtained from nuclear forward scattering of synchrotron radiation (NFS). The NFS technique enables a fast data accumulation resulting in high time resolution of in situ experiments. The results suggest a reaction mechanism, involving Fe(V) and Fe(IV) species, in the thermal decomposition of K2FeO4 to KFeO2. The present study opens up an approach to exploring the unambiguous identification of Fe(VI), Fe(V), Fe(IV), and Fe(III) in electron-transfer reaction mechanisms of ferrates in solid and aqueous phase systems.
