RESUMO
The mobility and bioavailability of phosphate in paddy soils are closely coupled to redox-driven Fe-mineral dynamics. However, the role of phosphate during Fe-mineral dissolution and transformations in soils remains unclear. Here, we investigated the transformations of ferrihydrite and lepidocrocite and the effects of phosphate pre-adsorbed to ferrihydrite during a 16-week field incubation in a flooded sandy rice paddy soil in Thailand. For the deployment of the synthetic Fe-minerals in the soil, the minerals were contained in mesh bags either in pure form or after mixing with soil material. In the latter case, the Fe-minerals were labeled with 57Fe to allow the tracing of minerals in the soil matrix with 57Fe Mössbauer spectroscopy. Porewater geochemical conditions were monitored, and changes in the Fe-mineral composition were analyzed using 57Fe Mössbauer spectroscopy and/or X-ray diffraction analysis. Reductive dissolution of ferrihydrite and lepidocrocite played a minor role in the pure mineral mesh bags, while in the 57Fe-mineral-soil mixes more than half of the minerals was dissolved. The pure ferrihydrite was transformed largely to goethite (82-85%), while ferrihydrite mixed with soil only resulted in 32% of all remaining 57Fe present as goethite after 16 weeks. In contrast, lepidocrocite was only transformed to 12% goethite when not mixed with soil, but 31% of all remaining 57Fe was found in goethite when it was mixed with soil. Adsorbed phosphate strongly hindered ferrihydrite transformation to other minerals, regardless of whether it was mixed with soil. Our results clearly demonstrate the influence of the complex soil matrix on Fe-mineral transformations in soils under field conditions and how phosphate can impact Fe oxyhydroxide dynamics under Fe reducing soil conditions.
Assuntos
Compostos Férricos , Oryza , Fosfatos , Solo , Oryza/química , Fosfatos/química , Solo/química , Adsorção , Compostos Férricos/química , Minerais/química , Espectroscopia de Mossbauer , Ferro/química , OxirreduçãoRESUMO
Iron minerals in soils and sediments play important roles in many biogeochemical processes and therefore influence the cycling of major and trace elements and the fate of pollutants in the environment. However, the kinetics and pathways of Fe mineral recrystallization and transformation processes under environmentally relevant conditions are still elusive. Here, we present a novel approach enabling us to follow the transformations of Fe minerals added to soils or sediments in close spatial association with complex solid matrices including other minerals, organic matter, and microorganisms. Minerals enriched with the stable isotope 57Fe are mixed with soil or sediment, and changes in Fe speciation are subsequently studied by 57Fe Mössbauer spectroscopy, which exclusively detects 57Fe. In this study, 57Fe-labeled ferrihydrite was synthesized, mixed with four soils differing in chemical and physical properties, and incubated for 12+ weeks under anoxic conditions. Our results reveal that the formation of crystalline Fe(III)(oxyhydr)oxides such as lepidocrocite and goethite was strongly suppressed, and instead formation of a green rust-like phase was observed in all soils. These results contrast those from Fe(II)-catalyzed ferrihydrite transformation experiments, where formation of lepidocrocite, goethite, and/or magnetite often occurs. The presented approach allows control over the composition and crystallinity of the initial Fe mineral, and it can be easily adapted to other experimental setups or Fe minerals. It thus offers great potential for future investigations of Fe mineral transformations in situ under environmentally relevant conditions, in both the laboratory and the field.
Assuntos
Compostos Férricos , Ferro , Compostos Férricos/química , Solo , Espectroscopia de Mossbauer , Oxirredução , Minerais/químicaRESUMO
Iron is an essential cofactor for several metabolic processes, including the generation of ATP in mitochondria, which is required for axonal function and regeneration. However, it is not known how mitochondria in long axons, such as those in sciatic nerves, acquire iron in vivo Because of their close proximity to axons, Schwann cells are a likely source of iron for axonal mitochondria in the PNS. Here we demonstrate the critical role of iron in promoting neurite growth in vitro using iron chelation. We also show that Schwann cells express the molecular machinery to release iron, namely, the iron exporter, ferroportin (Fpn) and the ferroxidase ceruloplasmin (Cp). In Cp KO mice, Schwann cells accumulate iron because Fpn requires to partner with Cp to export iron. Axons and Schwann cells also express the iron importer transferrin receptor 1 (TfR1), indicating their ability for iron uptake. In teased nerve fibers, Fpn and TfR1 are predominantly localized at the nodes of Ranvier and Schmidt-Lanterman incisures, axonal sites that are in close contact with Schwann cell cytoplasm. We also show that lack of iron export from Schwann cells in Cp KO mice reduces mitochondrial iron in axons as detected by reduction in mitochondrial ferritin, affects localization of axonal mitochondria at the nodes of Ranvier and Schmidt-Lanterman incisures, and impairs axonal regeneration following sciatic nerve injury. These finding suggest that Schwann cells contribute to the delivery of iron to axonal mitochondria, required for proper nerve repair.SIGNIFICANCE STATEMENT This work addresses how and where mitochondria in long axons in peripheral nerves acquire iron. We show that Schwann cells are a likely source as they express the molecular machinery to import iron (transferrin receptor 1), and to export iron (ferroportin and ceruloplasmin [Cp]) to the axonal compartment at the nodes of Ranvier and Schmidt-Lanterman incisures. Cp KO mice, which cannot export iron from Schwann cells, show reduced iron content in axonal mitochondria, along with increased localization of axonal mitochondria at Schmidt-Lanterman incisures and nodes of Ranvier, and impaired sciatic nerve regeneration. Iron chelation in vitro also drastically reduces neurite growth. These data suggest that Schwann cells are likely to contribute iron to axonal mitochondria needed for axon growth and regeneration.
Assuntos
Axônios/metabolismo , Ferro/metabolismo , Mitocôndrias/metabolismo , Regeneração Nervosa/fisiologia , Células de Schwann/metabolismo , Neuropatia Ciática/fisiopatologia , Animais , Proteínas de Transporte de Cátions/metabolismo , Células Cultivadas , Ceruloplasmina/deficiência , Ceruloplasmina/metabolismo , Feminino , Gânglios Espinais/citologia , Quelantes de Ferro/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Crescimento Neuronal , RNA/biossíntese , Nós Neurofibrosos/metabolismo , Receptores da Transferrina/metabolismo , Nervo Isquiático/citologia , Nervo Isquiático/fisiologia , Células Receptoras Sensoriais/fisiologia , Transcrição GênicaRESUMO
Interactions between aqueous ferrous iron (Fe(II)) and secondary Fe oxyhydroxides catalyze mineral recrystallization and/or transformation processes in anoxic soils and sediments, where oxyanions, such as silicate, are abundant. However, the effect and the fate of silicate during Fe mineral recrystallization and transformation are not entirely understood and especially remain unclear for lepidocrocite. In this study, we reacted (Si-)ferrihydrite (Si/Fe = 0, 0.05, and 0.18) and (Si-)lepidocrocite (Si/Fe = 0 and 0.08) with isotopically labeled 57Fe(II) (Fe(II)/Fe(III) = 0.02 and 0.2) at pH 7 for up to 4 weeks. We followed Fe mineral transformations with X-ray diffraction and tracked Fe atom exchange by measuring aqueous and solid phase Fe isotope fractions. Our results show that the extent of ferrihydrite transformation in the presence of Fe(II) was strongly influenced by the solid phase Si/Fe ratio, while increasing the Fe(II)/Fe(III) ratio (from 0.02 to 0.2) had only a minor effect. The presence of silicate increased the thickness of newly formed lepidocrocite crystallites, and elemental distribution maps of Fe(II)-reacted Si-ferrihydrites revealed that much more Si was associated with the remaining ferrihydrite than with the newly formed lepidocrocite. Pure lepidocrocite underwent recrystallization in the low Fe(II) treatment and transformed to magnetite at the high Fe(II)/Fe(III) ratio. Adsorbed silicate inactivated the lepidocrocite surfaces, which strongly reduced Fe atom exchange and inhibited mineral transformation. Collectively, the results of this study demonstrate that Fe(II)-catalyzed Si-ferrihydrite transformation leads to the redistribution of silicate in the solid phase and the formation of thicker lepidocrocite platelets, while lepidocrocite transformation can be completely inhibited by adsorbed silicate. Therefore, silicate is an important factor to include when considering Fe mineral dynamics in soils under reducing conditions.
Assuntos
Compostos Férricos , Minerais , Catálise , Compostos Férricos/química , Óxido Ferroso-Férrico , Minerais/química , Oxirredução , Silicatos , Solo , ÁguaRESUMO
The microstructure of the materials constituting a metallic frictional contact strongly influence tribological performance. Being able to tailor friction and wear is challenging due to the complex microstructure evolution associated with tribological loading. Here, we investigate the effect of the strain distribution on these processes. High-purity copper plates were morphologically surface textured with two parallel rectangles - referred to as membranes - over the entire sample length by micro-milling. By keeping the width of these membranes constant and only varying their height, reciprocating tribological loading against sapphire discs resulted in different elastic and plastic strains. Finite element simulations were carried out to evaluate the strain distribution in the membranes. It was found that the maximum elastic strain increases with decreasing membrane stiffness. The coefficient of friction decreases with increasing membrane aspect ratio. By analyzing the microstructure and local crystallographic orientation, we found that both show less change with decreasing membrane stiffness.
RESUMO
BACKGROUND: General Practitioners' (GPs) readiness to implement screening and brief intervention (SBI) to treat patients with excessive alcohol consumption is low. Several studies identified crucial barriers such as insufficient financial reimbursement. In contrast to the barriers-account, we assume that low implementation readiness of GPs may be less attributed to external barriers but rather more so to inherent characteristics of SBI. To test our assumption, we conducted a vignette study assessing the GPs' readiness to implement SBI in comparison to a pharmacological intervention also designed for the treatment of excessive drinkers in relation to standard or above-standard financial reimbursement. According to our hypothesis GPs should be less ready to implement SBI regardless of financial reimbursement. METHODS: A convenience sample of GPs was recruited to answer the questionnaire. To assess the GPs' implementation readiness a 4-item 6-point Likert scale was developed and pretested. RESULTS: One hundred forty GPs completed the questionnaire. GPs were more ready to implement the pharmacological intervention than SBI, F(1,132) = 27.58, p > .001 (main effect). We found no effect for financial reimbursement, F(1,132) = 3.60, ns, and no interaction effect, F(1,132) = 2.20, ns. CONCLUSIONS: Further research should investigate more thoroughly the crucial characteristics of SBI to initiate a modification process finally leading to more effective primary care dependency prevention.
Assuntos
Intervenção em Crise , Clínicos Gerais , Consumo de Bebidas Alcoólicas , Atitude do Pessoal de Saúde , Estudos Transversais , Humanos , Atenção Primária à SaúdeRESUMO
Population-based studies on Staphylococcus aureus nasal colonization are scarce. We examined the prevalence, resistance, and molecular diversity of S. aureus in the general population in Northeast Germany. Nasal swabs were obtained from 3,891 adults in the large-scale population-based Study of Health in Pomerania (SHIP-TREND). Isolates were characterized using spa genotyping, as well as antibiotic resistance and virulence gene profiling. We observed an S. aureus prevalence of 27.2%. Nasal S. aureus carriage was associated with male sex and inversely correlated with age. Methicillin-resistant S. aureus (MRSA) accounted for 0.95% of the colonizing S. aureus strains. MRSA carriage was associated with frequent visits to hospitals, nursing homes, or retirement homes within the previous 24 months. All MRSA strains were resistant to multiple antibiotics. Most MRSA isolates belonged to the pandemic European hospital-acquired MRSA sequence type 22 (HA-MRSA-ST22) lineage. We also detected one livestock-associated MRSA ST398 (LA-MRSA-ST398) isolate, as well as six livestock-associated methicillin-susceptible S. aureus (LA-MSSA) isolates (clonal complex 1 [CC1], CC97, and CC398). spa typing revealed a diverse but also highly clonal S. aureus population structure. We identified a total of 357 spa types, which were grouped into 30 CCs or sequence types. The major seven CCs (CC30, CC45, CC15, CC8, CC7, CC22, and CC25) included 75% of all isolates. Virulence gene patterns were strongly linked to the clonal background. In conclusion, MSSA and MRSA prevalences and the molecular diversity of S. aureus in Northeast Germany are consistent with those of other European countries. The detection of HA-MRSA and LA-MRSA within the general population indicates possible transmission from hospitals and livestock, respectively, and should be closely monitored.
Assuntos
Portador Sadio/epidemiologia , Cavidade Nasal/microbiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/isolamento & purificação , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Portador Sadio/microbiologia , Análise por Conglomerados , Estudos de Coortes , Farmacorresistência Bacteriana , Feminino , Variação Genética , Genótipo , Técnicas de Genotipagem , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Tipagem Molecular , Prevalência , Fatores Sexuais , Infecções Estafilocócicas/microbiologia , Proteína Estafilocócica A/genética , Staphylococcus aureus/genética , Fatores de Virulência/genética , Adulto JovemRESUMO
We conducted a microarray study to identify genes that are differentially regulated in the spinal cords of mice with the inflammatory disease experimental autoimmune encephalomyelitis (EAE) relative to healthy mice. In total 181 genes with at least a two-fold increase in expression were identified, and most of these genes were associated with immune function. Unexpectedly, ceruloplasmin (Cp), a ferroxidase that converts toxic ferrous iron to its nontoxic ferric form and also promotes the efflux of iron from astrocytes in the CNS, was shown to be highly upregulated (13.2-fold increase) in EAE spinal cord. Expression of Cp protein is known to be increased in several neurological conditions, but the role of Cp regulation in CNS autoimmune disease is not known. To investigate this, we induced EAE in Cp gene knockout, heterozygous, and wild-type mice. Cp knockout mice were found to have slower disease evolution than wild-type mice (EAE days 13-17; P = 0.05). Interestingly, Cp knockout mice also exhibited a significant increase in the number of astrocytes with reactive morphology in early EAE compared with wild-type mice at the same stage of disease. CNS iron levels were not increased with EAE in these mice. Based on these observations, we propose that an increase in Cp expression could contribute to tissue damage in early EAE. In addition, endogenous CP either directly or indirectly inhibits astrocyte reactivity during early disease, which could also worsen early disease evolution.
Assuntos
Ceruloplasmina/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Animais , Western Blotting , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/patologia , TranscriptomaRESUMO
The Implicit Association Test (IAT, Greenwald et al., J. Pers. Soc. Psychol., 74, 1998, 1464) is a popular instrument for measuring attitudes and (stereotypical) biases. Greenwald et al. (Behav. Res. Methods, 54, 2021, 1161) proposed a concrete method for validating IAT stimuli: appropriate stimuli should be familiar and easy to classify - translating to rapid (response times <800 ms) and accurate (error < 10%) participant responses. We conducted three analyses to explore the theoretical and practical utility of these proposed validation criteria. We first applied the proposed validation criteria to the data of 15 IATs that were available via Project Implicit. A bootstrap approach with 10,000 'experiments' of 100 participants showed that 5.85% of stimuli were reliably valid (i.e., we are more than 95% confident that a stimulus will also be valid in a new sample of 18- to 25-year-old US participants). Most stimuli (78.44%) could not be reliably validated, indicating a less than 5% certainty in the outcome of stimulus (in)validity for a new sample of participants. We then explored how stimulus validity differs across IATs. Results show that only some stimuli are consistently (in)valid. Most stimuli show between-IAT variances, which indicate that stimulus validity differs across IAT contexts. In the final analysis, we explored the effect of stimulus type (images, nouns, names, adjectives) on stimulus validity. Stimulus type was a significant predictor of stimulus validity. Although images attain the highest stimulus validity, raw data show large differences within stimulus types. Together, the results indicate a need for revised validation criteria. We finish with practical recommendations for stimulus selection and (post-hoc) stimulus validation.
Assuntos
Associação , Atitude , Humanos , Adolescente , Adulto Jovem , Adulto , Tempo de ReaçãoRESUMO
While causal reasoning is a core facet of our cognitive abilities, its time-course has not received proper attention. As the duration of reasoning might prove crucial in understanding the underlying cognitive processes, we asked participants in two experiments to make probabilistic causal inferences while manipulating time pressure. We found that participants are less accurate under time pressure, a speed-accuracy-tradeoff, and that they respond more conservatively. Surprisingly, two other persistent reasoning errors-Markov violations and failures to explain away-appeared insensitive to time pressure. These observations seem related to confidence: Conservative inferences were associated with low confidence, whereas Markov violations and failures to explain were not. These findings challenge existing theories that predict an association between time pressure and all causal reasoning errors including conservatism. Our findings suggest that these errors should not be attributed to a single cognitive mechanism and emphasize that causal judgements are the result of multiple processes.
Assuntos
Resolução de Problemas , Pressão do Tempo , Humanos , Cognição , JulgamentoRESUMO
How iron is delivered to the CNS for myelination is not well understood. We assessed whether astrocytes can provide iron to cells in the CNS for remyelination. To study this we generated a conditional deletion of the iron efflux transporter ferroportin (Fpn) in astrocytes, and induced focal demyelination in the mouse spinal cord dorsal column by microinjection of lysophosphatidylcholine (LPC). Remyelination assessed by electron microscopy was reduced in astrocyte-specific Fpn knock-out mice compared with wild-type controls, as was proliferation of oligodendrocyte precursor cells (OPCs). Cell culture work showed that lack of iron reduces the ability of microglia to express cytokines (TNF-α and IL-1ß) involved in remyelination. Furthermore, astrocytes in culture express high levels of FGF-2 in response to IL-1ß, and IGF-1 in response to TNF-α stimulation. FGF-2 and IGF-1 are known to be important for myelination. Reduction in IL-1ß and IGF-1 were also seen in astrocyte-specific Fpn knock-out mice after LPC-induced demyelination. These data suggest that iron efflux from astrocytes plays a role in remyelination by either direct effects on OPCs or indirectly by affecting glial activation.
Assuntos
Astrócitos/metabolismo , Ferro/metabolismo , Bainha de Mielina/fisiologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Knockout , Fibras Nervosas Mielinizadas/metabolismo , Oligodendroglia/metabolismoRESUMO
Iron (Fe) oxyhydroxides can be reductively dissolved or transformed under Fe reducing conditions, affecting mineral crystallinity and the sorption capacity for other elements. However, the pathways and rates at which these processes occur under natural soil conditions are still poorly understood. Here, we studied Fe oxyhydroxide transformations during reduction-oxidation cycles by incubating mesh bags containing ferrihydrite or lepidocrocite in paddy soil mesocosms for up to 12 weeks. To investigate the influence of close contact with the soil matrix, mesh bags were either filled with pure Fe minerals or with soil mixed with 57Fe-labeled Fe minerals. Three cycles of flooding (3 weeks) and drainage (1 week) were applied to induce soil redox cycles. The Fe mineral composition was analyzed with Fe K-edge X-ray absorption fine structure spectroscopy, X-ray diffraction analysis and/or 57Fe Mössbauer spectroscopy. Ferrihydrite and lepidocrocite in mesh bags without soil transformed to magnetite and/or goethite, likely catalyzed by Fe(II) released to the pore water by microbial Fe reduction in the surrounding soil. In contrast, 57Fe-ferrihydrite in mineral-soil mixes transformed to a highly disordered mixed-valence Fe(II)-Fe(III) phase, suggesting hindered transformation to crystalline Fe minerals. The 57Fe-lepidocrocite transformed to goethite and small amounts of the highly disordered Fe phase. The extent of reductive dissolution of minerals in 57Fe-mineral-soil mixes during anoxic periods increased with every redox cycle, while ferrihydrite and lepidocrocite precipitated during oxic periods. The results demonstrate that the soil matrix strongly impacts Fe oxyhydroxide transformations when minerals are in close spatial association or direct contact with other soil components. This can lead to highly disordered and reactive Fe phases from ferrihydrite rather than crystalline mineral products and promoted goethite formation from lepidocrocite.
Assuntos
Compostos Férricos , Minerais , Compostos Férricos/química , Minerais/química , Oxirredução , Óxido Ferroso-FérricoRESUMO
Accumulation of iron occurs in the CNS in several neurodegenerative diseases. Iron is essential for life but also has the ability to generate toxic free radicals if not properly handled. Iron homeostasis at the cellular level is therefore important to maintain proper cellular function, and its dysregulation can contribute to neurodegenerative diseases. Iron export, a key mechanism to maintain proper levels in cells, occurs via ferroportin, a ubiquitously expressed transmembrane protein that partners with a ferroxidase. A membrane-bound form of the ferroxidase ceruloplasmin is expressed by astrocytes in the CNS and regulates iron efflux. We now show that oligodendrocytes use another ferroxidase, called hephaestin, which was first identified in enterocytes in the gut. Mice with mutations in the hephaestin gene (sex-linked anemia mice) show iron accumulation in oligodendrocytes in the gray matter, but not in the white matter, and exhibit motor deficits. This was accompanied by a marked reduction in the levels of the paranodal proteins contactin-associated protein 1 (Caspr) and reticulon-4 (Nogo A). We show that the sparing of iron accumulation in white matter oligodendrocytes in sex-linked anemia mice is due to compensatory upregulation of ceruloplasmin in these cells. This was further confirmed in ceruloplasmin/hephaestin double-mutant mice, which show iron accumulation in both gray and white matter oligodendrocytes. These data indicate that gray and white matter oligodendrocytes can use different iron efflux mechanisms to maintain iron homeostasis. Dysregulation of such efflux mechanisms leads to iron accumulation in the CNS.
Assuntos
Ferro/metabolismo , Proteínas de Membrana/fisiologia , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Amielínicas/metabolismo , Oligodendroglia/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Proteínas de Transporte de Cátions/metabolismo , Moléculas de Adesão Celular Neuronais/metabolismo , Ceruloplasmina/genética , Ceruloplasmina/metabolismo , Feminino , Homeostase/genética , Homeostase/fisiologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Proteínas da Mielina/metabolismo , Proteínas Nogo , Ratos , Ratos Sprague-Dawley , Teste de Desempenho do Rota-Rod/métodos , Medula Espinal/metabolismo , Medula Espinal/ultraestruturaRESUMO
Toxoplasmosis is a rare but possibly underestimated complication following allogeneic stem cell transplantation with a high mortality rate. One reason might be the limitation of the diagnostic instruments relying mainly on imaging and molecular-based techniques. In this report, we present three cases of toxoplasmosis identified among 155 allograft recipients treated at Greifswald University Hospital. Widely disseminated toxoplasmosis was detected post-mortem in two patients allografted for high-risk multiple myeloma. Clinical signs suspicious for toxoplasmosis occurred after days +32 and +75, respectively. In one case, serology and conventional Toxoplasma gondii PCR, targeting the B1 gene, revealed negative results, while in the other patient, toxoplasmosis was not investigated. Both patients received pentamidine for Pneumocystis jirovecii pneumonia (PcP) prophylaxis. The third patient, a 68-year-old woman allografted for AML, developed cerebral toxoplasmosis from day +395 after allogeneic SCT with typical signs in magnetic resonance tomography. Toxoplasma DNA was amplified from one of two samples of cerebrospinal fluid. The patient died of disseminated toxoplasmosis despite immediate initiation of therapy. Retrospective comparative testing of clinical specimens by the conventional T. gondii PCR and by a real-time PCR targeting a 529-bp genomic fragment suggests a higher sensitivity of the latter method in our patients. In conclusion, we suggest a rigorous real-time PCR monitoring for high-risk patients or patients with signs of infections suspicious for toxoplasmosis, even though low-copy results are presently difficult to interpret. Our reported cases might also encourage the use of trimethoprim-sufmethoxazole instead of pentamidine for PcP prophylaxis in those patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Toxoplasmose/diagnóstico , Toxoplasmose/etiologia , Doença Aguda , Idoso , Estudos de Coortes , Evolução Fatal , Feminino , Doença Enxerto-Hospedeiro/complicações , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Transplante Homólogo/efeitos adversosRESUMO
Complex interactions between redox-driven element cycles in soils influence iron mineral transformation processes. The rates and pathways of iron mineral transformation processes have been studied intensely in model systems such as mixed suspensions, but transformation in complex heterogeneous porous media is not well understood. Here, mesh bags containing 0.5 g of ferrihydrite were incubated in five water-saturated paddy soils with contrasting microbial iron-reduction potential for up to twelve weeks. Using X-ray diffraction analysis, we show near-complete transformation of the ferrihydrite to lepidocrocite and goethite within six weeks in the soil with the highest iron(II) release, and slower transformation with higher ratios of goethite to lepidocrocite in soils with lower iron(II) release. In the least reduced soil, no mineral transformations were observed. In soils where ferrihydrite transformation occurred, the transformation rate was one to three orders of magnitude slower than transformation in comparable mixed-suspension studies. To interpret the spatial distribution of ferrihydrite and its transformation products, we developed a novel application of confocal micro-Raman spectroscopy in which we identified and mapped minerals on selected cross sections of mesh bag contents. After two weeks of flooded incubation, ferrihydrite was still abundant in the core of some mesh bags, and as a rim at the mineral-soil interface. The reacted outer core contained unevenly mixed ferrihydrite, goethite and lepidocrocite on the micrometre scale. The slower rate of transformation and uneven distribution of product minerals highlight the influence of biogeochemically complex matrices and diffusion processes on the transformation of minerals, and the importance of studying iron mineral transformation in environmental media.
Assuntos
Compostos Férricos , Solo , Compostos Férricos/química , Minerais/química , Ferro/química , Oxirredução , Água , Compostos FerrososRESUMO
Amyotrophic lateral sclerosis (ALS), characterized by degeneration of spinal motor neurons, consists of sporadic and familial forms. One cause of familial ALS is missense mutations in the superoxide dismutase 1 (SOD1) gene. Iron accumulation occurs in the CNS of both forms of ALS; however, its contribution to the pathogenesis of ALS is not known. We examined the role of iron in a transgenic mouse line overexpressing the human SOD1(G37R) mutant. We show that multiple mechanisms may underlie the iron accumulation in neurons and glia in SOD1(G37R) transgenic mice. These include dysregulation of proteins involved in iron influx and sensing of intracellular iron; iron accumulation in ventral motor neurons secondary to blockage of anterograde axonal transport; and increased mitochondrial iron load in neurons and glia. We also show that treatment of SOD1(G37R) mice with an iron chelator extends life span by 5 weeks, accompanied by increased survival of spinal motor neurons and improved locomotor function. These data suggest that iron chelator therapy might be useful for the treatment of ALS.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/patologia , Sistema Nervoso Central/metabolismo , Ferro/metabolismo , Fatores Etários , Aldeídos/uso terapêutico , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/genética , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 1/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Ferrozina , Regulação da Expressão Gênica/genética , Proteína Glial Fibrilar Ácida/metabolismo , Homeostase , Hidrazonas/uso terapêutico , Indóis , Quelantes de Ferro/uso terapêutico , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/metabolismo , Mutação , Fosfopiruvato Hidratase/metabolismo , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo , Neuropatia Ciática/metabolismo , Superóxido Dismutase/genéticaRESUMO
In this paper we argue that for the (probabilistic) interpretation of generic sentences of the form "Gs are f," three types of alternatives play a role: (i) alternative features of f, (ii) alternative groups, or kinds, of G, and (iii) alternative causal background factors. In the first part of this paper we argue for the relevance of these alternatives. In the second part, we describe the results of some experiments that empirically tested in particular the second use of alternatives.
RESUMO
N-Terminal glutaminyl and glutamyl residues of peptides and proteins tend to form pyroglutamic acid (pGlu) by intramolecular cylization. The rate constants for spontaneous cyclization of glutamine (10(-6) s(-1)) and glutamic acid (10(-9) s(-1)) in aqueous solution differ by approximately 3 orders of magnitude at pH 6.5. Glutaminyl cyclases (QCs) from plants and mammals accelerate pGlu formation. Human QC exhibits a rate enhancement of 2.2 x 10(5) for glutamate cyclization, approximately 2 orders of magnitude lower than that of the corresponding N-terminal glutaminyl reaction. Thus, glutaminyl cyclases are enzymes with only modest specificity for cyclization of their primary glutaminyl substrates and may provide a link between glutamate cyclization and pathophysiology.
Assuntos
Aminoaciltransferases/química , Amiloide/química , Glutamina/química , Doença de Alzheimer/enzimologia , Doença de Alzheimer/fisiopatologia , Aminoaciltransferases/metabolismo , Amiloide/metabolismo , Animais , Catálise , Ciclização , Glutamina/metabolismo , Humanos , Especificidade por SubstratoRESUMO
Modified amyloid beta (Abeta) peptides represent major constituents of the amyloid deposits in Alzheimer's disease and Down's syndrome. In particular, N-terminal pyroglutamate (pGlu) following truncation renders Abeta more stable, increases hydrophobicity and the aggregation velocity. Recent evidence based on in vitro studies suggests that the cyclization of glutamic acid, leading to pGlu-Abeta, is catalyzed by the enzyme glutaminyl cyclase (QC) following limited proteolysis of Abeta at the N-terminus. Here, we studied the pGlu-formation by rat QC in vitro as well as after microinjection of Abeta(1-40) and Abeta(3-40) into the rat cortex in vivo/in situ with and without pharmacological QC inhibition. Significant pGlu-Abeta formation was observed following injection of Abeta(3-40) after 24 h, indicating a catalyzed process. The generation of pGlu-Abeta from Abeta(3-40) was significantly inhibited by intracortical microinjection of a QC inhibitor. The study provides first evidence that generation of pGlu-Abeta is a QC-catalyzed process in vivo. The approach per se offers a strategy for a rapid evaluation of compounds targeting a reduction of pGlu formation at the N-terminus of amyloid peptides.
Assuntos
Aminoaciltransferases/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral/enzimologia , Hipocampo/enzimologia , Ácido Pirrolidonocarboxílico/metabolismo , Aminoaciltransferases/química , Aminoaciltransferases/genética , Aminoaciltransferases/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Animais , Linhagem Celular , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Inibidores Enzimáticos/administração & dosagem , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Microinjeções , Ácido Pirrolidonocarboxílico/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Homologia de Sequência de AminoácidosRESUMO
Invasive aspergillosis (IA) is a serious hazard to high-risk haematological patients. There are increasing reports of azole-resistant Aspergillus spp. This study assessed the epidemiology of IA and azole-resistant Aspergillus spp. in patients with acute leukaemia in Germany. A prospective multicentre cohort study was performed in German haematology/oncology centres. The incidence of probable and proven aspergillosis according to the revised EORTC/MSG criteria was assessed for all patients with acute leukaemia [acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL)]. Cases were documented into a web-based case report form, and centres provided data on standards regarding prophylactic and diagnostic measures. Clinical isolates were screened centrally for azole resistance and, if applicable, underlying resistance mechanisms were analysed. Between September 2011 and December 2013, 179 cases of IA [6 proven (3.4%) and 173 probable (96.6%)] were diagnosed in 3067 patients with acute leukaemia. The incidence of IA was 6.4% among 2440 AML patients and 3.8% among 627 ALL patients. Mortality at Day 84 was 33.8% (49/145) and attributable mortality was 26.9% (39/145). At Day 84, 53 patients (29.6%) showed a complete response, 25 (14.0%) a partial response and 17 (9.5%) a deterioration or failure. A total of 77 clinical Aspergillus fumigatus isolates were collected during the study period. Two episodes of azole-resistant IA (1.1%) were caused by a TR/L98H mutation in the cyp51A gene. With only two cases of IA due to azole-resistant A. fumigatus, a change of antifungal treatment practices in Germany does not appear warranted currently.