RESUMO
PURPOSE: In any MR experiment, the bulk magnetization acts on itself, caused by the induced current in the RF receiver circuit that generates an oscillating damping field. This effect, known as "radiation damping" (RD), is usually weak and, therefore, unconsidered in MRI, but can affect quantitative studies performed with dedicated coils that provide a high SNR. The current work examined RD in a setup for investigations of small tissue specimens including a quantitative characterization of the spin-coil system. THEORY AND METHODS: A custom-made Helmholtz coil (radius and spacing 16 mm) was interfaced to a transmit-receive (Tx/Rx) switch with integrated passive feedback for modulation or suppression of RD similar to preamplifier decoupling. Pulse sequences included pulse-width arrays to demonstrate the absence/ presence of RD and difference techniques employing gradient pulses or composite RF pulses to quantify RD effects during free precession and transmission, respectively. Experiments were performed at 3T in small samples of MnCl2 solution. RESULTS: Significant RD effects may impact RF pulse application and evolution periods. Effective damping time constants were comparable to typical T2 * times or echo spacings in multi-echo sequences. Measurements of the phase relation showed that deviations from the commonly assumed 90° angle between the damping field and the transverse magnetization may occur. CONCLUSION: Radiation damping may affect the accuracy of quantitative MR measurements performed with dedicated RF coils. Efficient mitigation can be achieved hardware-based or by appropriate consideration in the pulse sequence.
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Imageamento por Ressonância Magnética , Ondas de Rádio , Imageamento por Ressonância Magnética/métodos , Imagens de FantasmasRESUMO
Cell membranes and macromolecules or paramagnetic compounds interact with water proton spins, which modulates magnetic resonance imaging (MRI) contrast providing information on tissue composition. For a further investigation, quantitative magnetization transfer (qMT) parameters (at 3T), including the ratio of the macromolecular and water proton pools, F, and the exchange-rate constant as well as the (observed) longitudinal and the effective transverse relaxation rates (at 3T and 7T), R1obs and R2*, respectively, were measured at high spatial resolution (200 µm) in a slice of fixed marmoset brain and compared to histology results obtained with Gallyas' myelin stain and Perls' iron stain. R1obs and R2* were linearly correlated with the iron content for the entire slice, whereas distinct differences were obtained between gray and white matter for correlations of relaxometry and qMT parameters with myelin content. The combined results suggest that the macromolecular pool interacting with water consists of myelin and (less efficient) non-myelin contributions. Despite strong correlation of F and R1obs, none of these parameters was uniquely specific to myelination. Due to additional sensitivity to iron stores, R1obs and R2* were more sensitive for depicting microstructural differences between cortical layers than F.
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Callithrix , Prótons , Animais , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Bainha de Mielina/metabolismo , Ferro/metabolismo , ÁguaRESUMO
Uncovering brain-tissue microstructure including axonal characteristics is a major neuroimaging research focus. Within this scope, anisotropic properties of magnetic susceptibility in white matter have been successfully employed to estimate primary axonal trajectories using mono-tensorial models. However, anisotropic susceptibility has not yet been considered for modeling more complex fiber structures within a voxel, such as intersecting bundles, or an estimation of orientation distribution functions (ODFs). This information is routinely obtained by high angular resolution diffusion imaging (HARDI) techniques. In applications to fixed tissue, however, diffusion-weighted imaging suffers from an inherently low signal-to-noise ratio and limited spatial resolution, leading to high demands on the performance of the gradient system in order to mitigate these limitations. In the current work, high angular resolution susceptibility imaging (HARSI) is proposed as a novel, phase-based methodology to estimate ODFs. A multiple gradient-echo dataset was acquired in an entire fixed chimpanzee brain at 61 orientations by reorienting the specimen in the magnetic field. The constant solid angle method was adapted for estimating phase-based ODFs. HARDI data were also acquired for comparison. HARSI yielded information on whole-brain fiber architecture, including identification of peaks of multiple bundles that resembled features of the HARDI results. Distinct differences between both methods suggest that susceptibility properties may offer complementary microstructural information. These proof-of-concept results indicate a potential to study the axonal organization in post-mortem primate and human brain at high resolution.
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Encéfalo , Substância Branca , Animais , Humanos , Encéfalo/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Substância Branca/diagnóstico por imagem , Neuroimagem , PrimatasRESUMO
PURPOSE: To develop a postprocessing algorithm that corrects geometric distortions due to spatial variations of the static magnetic field amplitude, B0 , and effects from relaxation during signal acquisition in EPI. THEORY AND METHODS: An analytic, complex point-spread function is deduced for k-space trajectories of EPI variants and applied to corresponding acquisitions in a resolution phantom and in human volunteers at 3 T. With the analytic point-spread function and experimental maps of B0 (and, optionally, the effective transverse relaxation time, T2* ) as input, a point-spread function matrix operator is devised for distortion correction by a Thikonov-regularized deconvolution in image space. The point-spread function operator provides additional information for an appropriate correction of the signal intensity distribution. A previous image combination algorithm for acquisitions with opposite phase blip polarities is adapted to the proposed method to recover destructively interfering signal contributions. RESULTS: Applications of the proposed deconvolution-based distortion correction ("DecoDisCo") algorithm demonstrate excellent distortion corrections and superior performance regarding the recovery of an undistorted intensity distribution in comparison to a multifrequency reconstruction. Examples include full and partial Fourier standard EPI scans as well as double-shot center-out trajectories. Compared with other distortion-correction approaches, DecoDisCo permits additional deblurring to obtain sharper images in cases of significant T2* effects. CONCLUSION: Robust distortion corrections in EPI acquisitions are feasible with high quality by regularized deconvolution with an analytic point-spread function. The general algorithm, which is publicly released on GitHub, can be straightforwardly adapted for specific EPI variants or other acquisition schemes.
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Artefatos , Imagem Ecoplanar , Algoritmos , Encéfalo/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imagens de FantasmasRESUMO
Despite recent developments in process-based modeling of treatment wetlands (TW), the dynamic response of horizontal flow (HF) aerated wetlands to interruptions of aeration has not yet been modeled. In this study, the dynamic response of organic carbon and nitrogen removal to interruptions of aeration in an HF aerated wetland was investigated using a recently-developed numerical process-based model. Model calibration and validation were achieved using previously obtained data from pilot-scale experiments. Setting initial concentrations for anaerobic bacteria to high values (≈ 35-70 mg L-1) and including ammonia sorption was important to simulate the treatment performance of the experimental wetland in transition phases when aeration was switched off and on again. Even though steady-state air flow rate impacted steady-state soluble chemical oxygen demand (CODs), ammonia nitrogen (NH4-N) and oxidized nitrogen (NOx-N) concentration length profiles, it did not substantially affect corresponding effluent concentrations during aeration interruption. When comparing simulated with experimental results, it is most likely that extending the model to include mass transfer through the biofilm will allow to better explain the underlying experiments and to increase simulation accuracy. This study provides insights into the dynamic behavior of HF aerated wetlands and discusses assumptions and limitations of the modeling approach.
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Carbono/análise , Nitrogênio/análise , Eliminação de Resíduos Líquidos , Poluição da Água/estatística & dados numéricos , Áreas Alagadas , Análise da Demanda Biológica de Oxigênio , DesnitrificaçãoRESUMO
Bacterial coenzyme B12-dependent 2-hydroxyisobutyryl-CoA mutase (HCM) is a radical enzyme catalyzing the stereospecific interconversion of (S)-3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA. It consists of two subunits, HcmA and HcmB. To characterize the determinants of substrate specificity, we have analyzed the crystal structure of HCM from Aquincola tertiaricarbonis in complex with coenzyme B12 and the substrates (S)-3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA in alternative binding. When compared with the well studied structure of bacterial and mitochondrial B12-dependent methylmalonyl-CoA mutase (MCM), HCM has a highly conserved domain architecture. However, inspection of the substrate binding site identified amino acid residues not present in MCM, namely HcmA Ile(A90) and Asp(A117). Asp(A117) determines the orientation of the hydroxyl group of the acyl-CoA esters by H-bond formation, thus determining stereospecificity of catalysis. Accordingly, HcmA D117A and D117V mutations resulted in significantly increased activity toward (R)-3-hydroxybutyryl-CoA. Besides interconversion of hydroxylated acyl-CoA esters, wild-type HCM as well as HcmA I90V and I90A mutant enzymes could also isomerize pivalyl- and isovaleryl-CoA, albeit at >10 times lower rates than the favorite substrate (S)-3-hydroxybutyryl-CoA. The nonconservative mutation HcmA D117V, however, resulted in an enzyme showing high activity toward pivalyl-CoA. Structural requirements for binding and isomerization of highly branched acyl-CoA substrates such as 2-hydroxyisobutyryl- and pivalyl-CoA, possessing tertiary and quaternary carbon atoms, respectively, are discussed.
Assuntos
Acil Coenzima A/metabolismo , Proteínas de Bactérias/metabolismo , Cobamidas/metabolismo , Hidroxibutiratos/metabolismo , Transferases Intramoleculares/metabolismo , Acil Coenzima A/química , Acil Coenzima A/genética , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Betaproteobacteria/enzimologia , Betaproteobacteria/genética , Biocatálise , Domínio Catalítico , Cristalografia por Raios X , Transferases Intramoleculares/química , Transferases Intramoleculares/genética , Cinética , Metilmalonil-CoA Mutase/química , Metilmalonil-CoA Mutase/genética , Metilmalonil-CoA Mutase/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Multimerização Proteica , Estrutura Quaternária de Proteína , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Homologia de Sequência de Aminoácidos , Estereoisomerismo , Especificidade por SubstratoRESUMO
BACKGROUND: The integration of available early interventions and healthcare for families with children by practicing pediatricians has yet to be systematically established. For this reason, the Association of Statutory Health Insurance Physicians of Baden-Wuerttemberg established overarching, accredited, cross-system quality circles that serve to integrate all representatives of the healthcare system as well as child and youth welfare services. These quality circles are led by specially trained moderator tandems consisting of pediatricians and staff members from youth welfare services. OBJECTIVES: The goal was to evaluate the endpoints of the regional implementation of cross-system quality circles for early interventions in the state of Baden-Wuerttemberg as well as the feasibility of establishing long-term training programs for cross-system moderator tandems. METHODS: This was a noncontrolled, longitudinal study to prepare a yearly evaluation of the quality-circle assessments as well as to gather statistics on the training of the moderator tandems within the Association of Statutory Health Insurance Physicians of Baden-Wuerttemberg. RESULTS: A total of 59 moderator tandems were trained in nine separate training sessions within the project period from 2011 to 2015. Overall, 33 quality circles were founded. In 2015, 566 persons were participating in the respective circles. Over the course of the study between 26 and 33 of the 44 urban and rural districts in the state of Baden-Wuerttemberg had at least one quality circle dedicated to early interventions. Ten further circles are presently in the process of being founded; 29 moderators have yet to commence their activity or have withdrawn from the program. DISCUSSION: Between 59 and 81 % of the urban and rural districts implemented cross-system quality circles. The training of the moderator tandems proceeded without complications. Because of the dropout quota of the trained moderator tandems, systematic and continual training of new tandems proves to be necessary.
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Prestação Integrada de Cuidados de Saúde/estatística & dados numéricos , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/prevenção & controle , Participação nas Decisões/estatística & dados numéricos , Modelos Organizacionais , Serviços Preventivos de Saúde/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Alemanha/epidemiologia , Humanos , Lactente , Recém-Nascido , Relações Interprofissionais , Masculino , Participação do Paciente/estatística & dados numéricos , Prevalência , Fatores de Risco , Revisão da Utilização de Recursos de Saúde , Adulto JovemRESUMO
The recent discovery of a coenzyme B12-dependent acyl-coenzyme A (acyl-CoA) mutase isomerizing 3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA in the mesophilic bacterium Aquincola tertiaricarbonis L108 (N. Yaneva, J. Schuster, F. Schäfer, V. Lede, D. Przybylski, T. Paproth, H. Harms, R. H. Müller, and T. Rohwerder, J Biol Chem 287:15502-15511, 2012, http://dx.doi.org/10.1074/jbc.M111.314690) could pave the way for a complete biosynthesis route to the building block chemical 2-hydroxyisobutyric acid from renewable carbon. However, the enzyme catalyzes only the conversion of the stereoisomer (S)-3-hydroxybutyryl-CoA at reasonable rates, which seriously hampers an efficient combination of mutase and well-established bacterial poly-(R)-3-hydroxybutyrate (PHB) overflow metabolism. Here, we characterize a new 2-hydroxyisobutyryl-CoA mutase found in the thermophilic knallgas bacterium Kyrpidia tusciae DSM 2912. Reconstituted mutase subunits revealed highest activity at 55°C. Surprisingly, already at 30°C, isomerization of (R)-3-hydroxybutyryl-CoA was about 7,000 times more efficient than with the mutase from strain L108. The most striking structural difference between the two mutases, likely determining stereospecificity, is a replacement of active-site residue Asp found in strain L108 at position 117 with Val in the enzyme from strain DSM 2912, resulting in a reversed polarity at this binding site. Overall sequence comparison indicates that both enzymes descended from different prokaryotic thermophilic methylmalonyl-CoA mutases. Concomitant expression of PHB enzymes delivering (R)-3-hydroxybutyryl-CoA (beta-ketothiolase PhaA and acetoacetyl-CoA reductase PhaB from Cupriavidus necator) with the new mutase in Escherichia coli JM109 and BL21 strains incubated on gluconic acid at 37°C led to the production of 2-hydroxyisobutyric acid at maximal titers of 0.7 mM. Measures to improve production in E. coli, such as coexpression of the chaperone MeaH and repression of thioesterase II, are discussed.
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Acil Coenzima A/metabolismo , Bacillales/enzimologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Cobamidas/metabolismo , Transferases Intramoleculares/química , Transferases Intramoleculares/metabolismo , Acil Coenzima A/química , Bacillales/química , Bacillales/genética , Bacillales/metabolismo , Proteínas de Bactérias/genética , Catálise , Estabilidade Enzimática , Transferases Intramoleculares/genética , Estereoisomerismo , Especificidade por SubstratoRESUMO
The yeast Yarrowia lipolytica is able to produce high amounts of several organic acids such as pyruvic, citric, isocitric, alpha-ketoglutaric, and succinic acid. Here we report on the influence of the reduced activity of succinate dehydrogenase in Y. lipolytica on its ability to produce succinate. The recombinant strains Y. lipolytica H222-AZ1 and H222-AZ2 were created by exchange of the native promoter of the succinate dehydrogenase subunit 2 encoding gene by inducible promoters. During the cultivation of the strain Y. lipolytica H222-AZ1 in shaking flask experiments, it was found that the promoter exchange resulted in an increase in succinic acid (SA) production. Moreover, it was found that the production of SA depends on an additional limitation of oxygen. Fed-batch cultivations in 1-l bioreactors confirmed this fundamental finding. Y. lipolytica H222-AZ1 produced 2 g l(-1) of SA with oxygen supply and 9.2 g l(-1) under the limitation of oxygen after 165 h. By using a less active promoter in Y. lipolytica H222-AZ2, the production of SA was increased to 25 g l(-1) with a productivity of 0.152 g (l*h)(-1) and a selectivity of 67 % after 165 h. Yields of 2.39 g SA per gram biomass and 0.26 g SA per gram glycerol were found.
Assuntos
Oxigênio/metabolismo , Ácido Succínico/metabolismo , Yarrowia/metabolismo , Técnicas de Cultura Celular por Lotes , Reatores Biológicos/microbiologia , Expressão Gênica , Engenharia Metabólica , Regiões Promotoras Genéticas , Recombinação Genética , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismo , Yarrowia/enzimologia , Yarrowia/genética , Yarrowia/crescimento & desenvolvimentoRESUMO
Current manufacturing of most bulk chemicals through petrochemical routes considerably contributes to common concerns over the depletion of fossil carbon sources and greenhouse gas emissions. Sustainable future production of commodities thus requires the shift to renewable feedstocks in combination with established or newly developed synthesis routes. In this study, the potential of Cupriavidus necator H16 for autotrophic synthesis of the building block chemical 2-hydroxyisobutyric acid (2-HIBA) is evaluated. A novel biosynthetic pathway was implemented by heterologous expression of the 2-hydroxyisobutyryl-coenzyme A (2-HIB-CoA) mutase from Aquincola tertiaricarbonis L108, relying on a main intermediate of strain H16's C4 overflow metabolism, 3-hydroxybutyryl-CoA. The intention was to direct the latter to 2-HIBA instead or in addition to poly-3-hydroxybutyrate (PHB). Autotrophic growth and 2-HIBA (respectively, PHB) synthesis of wild-type and PHB-negative mutant strains were investigated producing maximum 2-HIBA titers of 3.2 g L(-1) and maximum specific 2-HIBA synthesis rates (q 2-HIBA) of about 16 and 175 µmol g(-1) h(-1), respectively. The obtained specific productivity was the highest reported to date for mutase-dependent 2-HIBA synthesis from heterotrophic and autotrophic substrates. Furthermore, expression of a G protein chaperone (MeaH) in addition to the 2-HIB-CoA mutase subunits yielded improved productivity. Analyzing the inhibition of growth and product synthesis due to substrate availability and product accumulation revealed a strong influence of 2-HIBA, when cells were cultivated at high titers. Nevertheless, the presented results imply that at the time the autotrophic synthesis route is superior to thus far established heterotrophic routes for production of 2-HIBA with C. necator.
Assuntos
Dióxido de Carbono/metabolismo , Cupriavidus necator/metabolismo , Hidrogênio/metabolismo , Hidroxibutiratos/metabolismo , Transferases Intramoleculares/metabolismo , Engenharia Metabólica , Oxigênio/metabolismo , Vias Biossintéticas/genética , Cupriavidus necator/genética , Expressão Gênica , Transferases Intramoleculares/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Planners and decision-makers in the wastewater sector are often confronted with the problem of identifying adequate development strategies and most suitable finance schemes for decentralized wastewater infrastructure. This paper research has focused on providing an approach in support of such decision-making. It is based on basic principles that stand for an integrated perspective towards sustainable wastewater management. We operationalize these principles by means of a geographic information system (GIS)-based approach 'Assessment of Local Lowest-Cost Wastewater Solutions'--ALLOWS. The main product of ALLOWS is the identification of cost-effective local wastewater management solutions for any given demographic and physical context. By using universally available input data the tool allows decision-makers to compare different wastewater solutions for any given wastewater situation. This paper introduces the ALLOWS-GIS tool. Its application and functionality are illustrated by assessing different wastewater solutions for two neighboring communities in rural Jordan.
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Sistemas de Informação Geográfica , Águas Residuárias/análise , Purificação da Água/métodos , Tomada de Decisões , Sistemas de Informação Geográfica/economia , Sistemas de Informação Geográfica/legislação & jurisprudência , Irã (Geográfico) , Jordânia , Política , População Rural , Purificação da Água/economia , Purificação da Água/legislação & jurisprudênciaRESUMO
Here the major upgrades of the femtoslicing facility at BESSYâ II (Khan et al., 2006) are reviewed, giving a tutorial on how elliptical-polarized ultrashort soft X-ray pulses from electron storage rings are generated at high repetition rates. Employing a 6â kHz femtosecond-laser system consisting of two amplifiers that are seeded by one Ti:Sa oscillator, the total average flux of photons of 100â fs duration (FWHM) has been increased by a factor of 120 to up to 10(6)â photons s(-1) (0.1% bandwidth)(-1) on the sample in the range from 250 to 1400â eV. Thanks to a new beamline design, a factor of 20 enhanced flux and improvements of the stability together with the top-up mode of the accelerator have been achieved. The previously unavoidable problem of increased picosecond-background at higher repetition rates, caused by `halo' photons, has also been solved by hopping between different `camshaft' bunches in a dedicated fill pattern (`3+1 camshaft fill') of the storage ring. In addition to an increased X-ray performance at variable (linear and elliptical) polarization, the sample excitation in pump-probe experiments has been considerably extended using an optical parametric amplifier that supports the range from the near-UV to the far-IR regime. Dedicated endstations covering ultrafast magnetism experiments based on time-resolved X-ray circular dichroism have been either upgraded or, in the case of time-resolved resonant soft X-ray diffraction and reflection, newly constructed and adapted to femtoslicing requirements. Experiments at low temperatures down to 6â K and magnetic fields up to 0.5â T are supported. The FemtoSpeX facility is now operated as a 24â h user facility enabling a new class of experiments in ultrafast magnetism and in the field of transient phenomena and phase transitions in solids.
RESUMO
Sleep problems are a well-known risk factor for work injuries, but less is known about which vulnerable populations are most at risk. The aims of this study were to investigate the association between sleep quality and the risk of work injury and to identify factors that may modify the association. A case-control study including 180 cases and 551 controls was conducted at the University Hospital in Basel, Switzerland, from 1 December 2009 to 30 June 2011. Data on work injuries and sleep quality were collected. Adjusted odds ratios and 95% confidence intervals of the association between sleep quality and work injury were estimated in multivariable logistic regression analyses and were stratified by hypothesized effect modifiers (age, gender, job risk, shift work, sleep duration and working hours). Poor sleep quality was associated significantly with work injury of any type (P < 0.05) and with being caught in particular (P < 0.05). The association between poor sleep quality and work injury was significantly higher for workers older than 30 years (odds ratio>30 1.30 versus odds ratio≤30 0.91, P < 0.01), sleeping 7 h or less per night (odds ratio≤7 1.17 versus odds ratio>7 0.79, P < 0.05) and working 50 h or more per week (odds ratio≥50 1.79 versus odd ratio<50 1.10, P < 0.01). Work injury risk increased with increasing severity of sleep problems (P < 0.05). Prior work injury frequency increased with decreasing sleep quality (P < 0.05). Older age, short sleep duration and long working hours may enhance the risk of work injuries associated with sleep quality.
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Acidentes de Trabalho/estatística & dados numéricos , Sono/fisiologia , Adolescente , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fatores Sexuais , Suíça/epidemiologia , Fatores de Tempo , Tolerância ao Trabalho Programado/fisiologia , Tolerância ao Trabalho Programado/psicologia , Adulto JovemRESUMO
Delftia acidovorans MC1071 can productively degrade R-2-(2,4-dichlorophenoxy)propionate (R-2,4-DP) but not 2,4-dichlorophenoxyacetate (2,4-D) herbicides. This work demonstrates adaptation of MC1071 to degrade 2,4-D in a model two-dimensional porous medium (referred to here as a micromodel). Adaptation for 2,4-D degradation in the 2 cm-long micromodel occurred within 35 days of exposure to 2,4-D, as documented by substrate removal. The amount of 2,4-D degradation in the adapted cultures in two replicate micromodels (~10 and 20 % over 142 days) was higher than a theoretical maximum (4 %) predicted using published numerical simulation methods, assuming instantaneous biodegradation and a transverse dispersion coefficient obtained for the same pore structure without biomass present. This suggests that the presence of biomass enhances substrate mixing. Additional evidence for adaptation was provided by operation without R-2,4-DP, where degradation of 2,4-D slowly decreased over 20 days, but was restored almost immediately when R-2,4-DP was again provided. Compared to suspended growth systems, the micromodel system retained the ability to degrade 2,4-D longer in the absence of R-2,4-DP, suggesting slower responses and greater resilience to fluctuations in substrates might be expected in the soil environment than in a chemostat.
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Ácido 2,4-Diclorofenoxiacético/metabolismo , Adaptação Fisiológica , Delftia acidovorans/metabolismo , Microfluídica , Ácido 2,4-Diclorofenoxiacético/química , Técnicas de Cultura Celular por Lotes , Biodegradação Ambiental , Herbicidas/metabolismo , Porosidade , Especificidade por SubstratoRESUMO
A variation of the longitudinal relaxation time T 1 in brain regions that differ in their main fiber direction has been occasionally reported, however, with inconsistent results. Goal of the present study was to clarify such inconsistencies, and the origin of potential T 1 orientation dependence, by applying direct sample rotation and comparing the results from different approaches to measure T 1 . A section of fixed porcine spinal cord white matter was investigated at 3 T with variation of the fiber-to-field angle θ FB . The experiments included one-dimensional inversion-recovery, MP2RAGE, and variable flip-angle T 1 measurements at 22 °C and 36 °C as well as magnetization-transfer (MT) and diffusion-weighted acquisitions. Depending on the technique, different degrees of T 1 anisotropy (between 2 and 10%) were observed as well as different dependencies on θ FB (monotonic variation or T 1 maximum at 30-40°). More pronounced anisotropy was obtained with techniques that are more sensitive to MT effects. Furthermore, strong correlations of θ FB -dependent MT saturation and T 1 were found. A comprehensive analysis based on the binary spin-bath model for MT revealed an interplay of several orientation-dependent parameters, including the transverse relaxation times of the macromolecular and the water pool as well as the longitudinal relaxation time of the macromolecular pool.
Assuntos
Medula Espinal , Água , Substância Branca , Animais , Substância Branca/diagnóstico por imagem , Substância Branca/fisiologia , Suínos , Anisotropia , Medula Espinal/fisiologia , Prótons , RotaçãoRESUMO
The application of functional magnetic resonance imaging (fMRI) to the human spinal cord is still a relatively small field of research and faces many challenges. Here we aimed to probe the limitations of task-based spinal fMRI at 3T by investigating the reliability of spinal cord blood oxygen level dependent (BOLD) responses to repeated nociceptive stimulation across two consecutive days in 40 healthy volunteers. We assessed the test-retest reliability of subjective ratings, autonomic responses, and spinal cord BOLD responses to short heat pain stimuli (1s duration) using the intraclass correlation coefficient (ICC). At the group level, we observed robust autonomic responses as well as spatially specific spinal cord BOLD responses at the expected location, but no spatial overlap in BOLD response patterns across days. While autonomic indicators of pain processing showed good-to-excellent reliability, both ß-estimates and z-scores of task-related BOLD responses showed poor reliability across days in the target region (gray matter of the ipsilateral dorsal horn). When taking into account the sensitivity of gradient-echo echo planar imaging (GE-EPI) to draining vein signals by including the venous plexus in the analysis, we observed BOLD responses with fair reliability across days. Taken together, these results demonstrate that heat pain stimuli as short as one second are able to evoke a robust and spatially specific BOLD response, which is however strongly variable within participants across time, resulting in low reliability in the dorsal horn gray matter. Further improvements in data acquisition and analysis techniques are thus necessary before event-related spinal cord fMRI as used here can be reliably employed in longitudinal designs or clinical settings.
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The prevalence of anabolic androgenic steroids (AAS) is rising, especially in recreational sports and the general population. While body image significantly influences AAS use, gender differences remain unclear. We examined gender-related connections between AAS use, body image, eating behavior, and physical activity. Following PRISMA guidelines, we analyzed 22 studies: 14 with male-only samples, 5 mixed-gender, 2 with sexual and gender minorities, and 1 with a female-only sample. FINDINGS: confirm body image as a key predictor of AAS use. Though AAS use correlates with eating disorders, outcomes vary by context; for instance, no discernible difference in eating behavior was observed between AAS users and non-users in bodybuilding. Physical activity findings varied, with some studies showing no significant differences between AAS users and non-users. Due to limited gender-comparison studies, conclusive gender-related differences cannot be drawn. This systematic review underscores the complex interplay between AAS use, body image, eating behavior, and physical activity, emphasizing the necessity for further research to develop targeted interventions for diverse populations, addressing AAS-related concerns and promoting overall well-being.
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Imagem Corporal , Exercício Físico , Comportamento Alimentar , Humanos , Comportamento Alimentar/efeitos dos fármacos , Anabolizantes/administração & dosagem , Anabolizantes/efeitos adversos , Masculino , Feminino , Caracteres Sexuais , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Esteróides Androgênicos AnabolizantesRESUMO
PURPOSE: Field-to-susceptibility inversion in quantitative susceptibility mapping (QSM) is ill-posed and needs numerical stabilization through either regularization or oversampling by acquiring data at three or more object orientations. Calculation Of Susceptibility through Multiple Orientations Sampling (COSMOS) is an established oversampling approach and regarded as QSM gold standard. It achieves a well-conditioned inverse problem, requiring rotations by 0°, 60° and 120° in the yz-plane. However, this is impractical in vivo, where head rotations are typically restricted to a range of ±25°. Non-ideal sampling degrades the conditioning with residual streaking artifacts whose mitigation needs further regularization. Moreover, susceptibility anisotropy in white matter is not considered in the COSMOS model, which may introduce additional bias. The current work presents a thorough investigation of these effects in primate brain. METHODS: Gradient-recalled echo (GRE) data of an entire fixed chimpanzee brain were acquired at 7 T (350 µm resolution, 10 orientations) including ideal COSMOS sampling and realistic rotations in vivo. Comparisons of the results included ideal COSMOS, in-vivo feasible acquisitions with 3-8 orientations and single-orientation iLSQR QSM. RESULTS: In-vivo feasible and optimal COSMOS yielded high-quality susceptibility maps with increased SNR resulting from averaging multiple acquisitions. COSMOS reconstructions from non-ideal rotations about a single axis required additional L2-regularization to mitigate residual streaking artifacts. CONCLUSION: In view of unconsidered anisotropy effects, added complexity of the reconstruction, and the general challenge of multi-orientation acquisitions, advantages of sub-optimal COSMOS schemes over regularized single-orientation QSM appear limited in in-vivo settings.
Assuntos
Algoritmos , Artefatos , Encéfalo , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Anisotropia , Encéfalo/diagnóstico por imagem , Animais , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Pan troglodytes , Mapeamento Encefálico/métodos , Substância Branca/diagnóstico por imagem , Dinâmica não Linear , Reprodutibilidade dos TestesRESUMO
Coenzyme B(12)-dependent acyl-CoA mutases are radical enzymes catalyzing reversible carbon skeleton rearrangements in carboxylic acids. Here, we describe 2-hydroxyisobutyryl-CoA mutase (HCM) found in the bacterium Aquincola tertiaricarbonis as a novel member of the mutase family. HCM specifically catalyzes the interconversion of 2-hydroxyisobutyryl- and (S)-3-hydroxybutyryl-CoA. Like isobutyryl-CoA mutase, HCM consists of a large substrate- and a small B(12)-binding subunit, HcmA and HcmB, respectively. However, it is thus far the only acyl-CoA mutase showing substrate specificity for hydroxylated carboxylic acids. Complete loss of 2-hydroxyisobutyric acid degradation capacity in hcmA and hcmB knock-out mutants established the central role of HCM in A. tertiaricarbonis for degrading substrates bearing a tert-butyl moiety, such as the fuel oxygenate methyl tert-butyl ether (MTBE) and its metabolites. Sequence analysis revealed several HCM-like enzymes in other bacterial strains not related to MTBE degradation, indicating that HCM may also be involved in other pathways. In all strains, hcmA and hcmB are associated with genes encoding for a putative acyl-CoA synthetase and a MeaB-like chaperone. Activity and substrate specificity of wild-type enzyme and active site mutants HcmA I90V, I90F, and I90Y clearly demonstrated that HCM belongs to a new subfamily of B(12)-dependent acyl-CoA mutases.
Assuntos
Acil Coenzima A/metabolismo , Proteínas de Bactérias/metabolismo , Hidroxibutiratos/metabolismo , Transferases Intramoleculares/metabolismo , Vitamina B 12/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Betaproteobacteria/enzimologia , Betaproteobacteria/genética , Biocatálise , Domínio Catalítico , Eletroforese em Gel de Poliacrilamida , Concentração de Íons de Hidrogênio , Hidroxibutiratos/química , Transferases Intramoleculares/genética , Isoleucina/genética , Isoleucina/metabolismo , Isomerismo , Cinética , Dados de Sequência Molecular , Mutação , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Homologia de Sequência de Aminoácidos , Espectrometria de Massas por Ionização por Electrospray , Especificidade por SubstratoRESUMO
Aerobic anoxygenic photosynthesis (AAP) is found in an increasing number of proteobacterial strains thriving in ecosystems ranging from extremely oligotrophic to eutrophic. Here, we have investigated whether the fuel oxygenate-degrading betaproteobacterium Aquincola tertiaricarbonis L108 can use AAP to compensate kinetic limitations at low heterotrophic substrate fluxes. In a fermenter experiment with complete biomass retention and also during chemostat cultivation, strain L108 was challenged with extremely low substrate feeding rates of tert-butyl alcohol (TBA), an intermediate of methyl tert-butyl ether (MTBE). Interestingly, formation of photosynthetic pigments, identified as bacteriochlorophyll a and spirilloxanthin, was only induced in growing cells at TBA feeding rates less than or equal to maintenance requirements observed under energy excess conditions. Growth continued at rates between 0.001 and 0.002 h(-1) even when the TBA feed was decreased to values close to 30â% of this maintenance rate. Partial sequencing of genomic DNA of strain L108 revealed a bacteriochlorophyll synthesis gene cluster (bchFNBHL) and photosynthesis regulator genes (ppsR and ppaA) typically found in AAP and other photosynthetic proteobacteria. The usage of light as auxiliary energy source enabling evolution of efficient degradation pathways for kinetically limited heterotrophic substrates and for lowering the threshold substrate concentration Smin at which growth becomes zero is discussed.