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1.
Radiographics ; 43(1): e220088, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36367822

RESUMO

Arterial spin labeling (ASL) is an emerging noninvasive MRI technique for assessing cerebral perfusion. An important advantage of ASL perfusion is the lack of a requirement for an exogenous tracer. ASL uses magnetically labeled water protons from arterial blood as an endogenous diffusible tracer. For this reason, ASL is an attractive perfusion imaging modality for children and for patients with contraindications or adverse reactions to gadolinium, patients with renal failure, and those who need repeated follow-up imaging. Another advantage of ASL is the possibility of quantifying cerebral blood flow, which provides an opportunity for comparative analysis among multiple longitudinal studies, unlike other MR perfusion techniques, which are semiquantitative and yield relative perfusion parameters. Advances in MRI technology and pulse sequence design have translated ASL beyond the research arena to successful clinical implementation. However, ASL is still underused in routine clinical practice. Some disadvantages of ASL include a lower signal-to-noise ratio and a longer acquisition time than those with dynamic susceptibility contrast-enhanced MRI. Additional factors limiting the use of ASL include variations in existing techniques and pulse sequence design, the complexity of implementation and postprocessing, insufficient experience with and/or knowledge of the potential clinical applications, and the absence of interpretation guidelines. The authors review the technical and physiologic basis of ASL perfusion, as well as artifacts, pitfalls, and its current clinical applications. A practical approach for interpreting ASL findings is also suggested.


Assuntos
Circulação Cerebrovascular , Angiografia por Ressonância Magnética , Criança , Humanos , Marcadores de Spin , Angiografia por Ressonância Magnética/métodos , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética/métodos , Artefatos
2.
Artigo em Inglês | MEDLINE | ID: mdl-36341843

RESUMO

INTRODUCTION: Schizophrenia-spectrum disorders (SSD) represent one of the leading causes of disability worldwide and are usually underpinned by neurodevelopmental brain abnormalities observed on a structural and functional level. Nuclear medicine imaging studies of cerebral blood flow (CBF) have already provided insights into the pathophysiology of these disorders. Recent developments in non-invasive MRI techniques such as arterial spin labeling (ASL) have allowed broader examination of CBF across SSD prompting us to conduct an updated literature review of MRI-based perfusion studies. In addition, we conducted a focused meta-analysis of whole brain studies to provide a complete picture of the literature on the topic. METHODS: A systematic OVID search was performed in Embase, MEDLINEOvid, and PsycINFO. Studies eligible for inclusion in the review involved: 1) individuals with SSD, first-episode psychosis or clinical-high risk for psychosis, or; 2) had healthy controls for comparison; 3) involved MRI-based perfusion imaging methods; and 4) reported CBF findings. No time span was specified for the database queries (last search: 08/2022). Information related to participants, MRI techniques, CBF analyses, and results were systematically extracted. Whole-brain studies were then selected for the meta-analysis procedure. The methodological quality of each included studies was assessed. RESULTS: For the systematic review, the initial Ovid search yielded 648 publications of which 42 articles were included, representing 3480 SSD patients and controls. The most consistent finding was that negative symptoms were linked to cortical fronto-limbic hypoperfusion while positive symptoms seemed to be associated with hyperperfusion, notably in subcortical structures. The meta-analysis integrated results from 13 whole-brain studies, across 426 patients and 401 controls, and confirmed the robustness of the hypoperfusion in the left superior and middle frontal gyri and right middle occipital gyrus while hyperperfusion was found in the left putamen. CONCLUSION: This updated review of the literature supports the implication of hemodynamic correlates in the pathophysiology of psychosis symptoms and disorders. A more systematic exploration of brain perfusion could complete the search of a multimodal biomarker of SSD.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Circulação Cerebrovascular , Imageamento por Ressonância Magnética , Marcadores de Spin
3.
Food Chem ; 402: 134354, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36191464

RESUMO

Deciphering interactions between bioactive protein and polyphenols are critical for designing and controlling functional protein-polyphenol complexes. Herein, using the site-directed spin labeled T4 lysozyme (T4L) and rosmarinic acid (RA) as a model system, we combined electron paramagnetic resonance spectra to investigate molecular interaction mechanism of the protein-polyphenol complexes in structural or conformational details. Experimental results show that molecular interactions between T4L and RA are a process from order to disorder. TEM images display that the complexes finally assemble into quasi-spherical colloidal particles. When T4L/RA ratio is 1:1, the complexes exhibit the optimized enzymatic and antioxidant dual-functionalities due to the synergetic effect and protection mechanism. However, with excess addition of RA, the enzymatic and antioxidant activities of the complexes started to attenuate because the catalytic active site and bioactive hydroxyl groups were buried. The revealed high-resolution interaction process could help better understand the corresponding alterations between structure and functionalities.


Assuntos
Muramidase , Polifenóis , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Muramidase/química , Antioxidantes , Marcadores de Spin , Domínio Catalítico , Relação Estrutura-Atividade
4.
Molecules ; 27(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364348

RESUMO

We present a new photoswitchable spin label for light-induced pulsed electron paramagnetic resonance dipolar spectroscopy (LiPDS), the photoexcited triplet state of erythrosin B (EB), which is ideal for biological applications. With this label, we perform an in-depth study of the orientational effects in dipolar traces acquired using the refocused laser-induced magnetic dipole technique to obtain information on the distance and relative orientation between the EB and nitroxide labels in a rigid model peptide, in good agreement with density functional theory predictions. Additionally, we show that these orientational effects can be averaged to enable an orientation-independent analysis to determine the distance distribution. Furthermore, we demonstrate the feasibility of these experiments above liquid nitrogen temperatures, removing the need for expensive liquid helium or cryogen-free cryostats. The variety of choices in photoswitchable spin labels and the affordability of the experiments are critical for LiPDS to become a widespread methodology in structural biology.


Assuntos
Eritrosina , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Marcadores de Spin , Temperatura
5.
Molecules ; 27(21)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36364453

RESUMO

Sterically shielded nitroxides, which demonstrate high resistance to bioreduction, are the spin labels of choice for structural studies inside living cells using pulsed EPR and functional MRI and EPRI in vivo. To prepare new sterically shielded nitroxides, a reaction of cyclic nitrones, including various 1-pyrroline-1-oxides, 2,5-dihydroimidazole-3-oxide and 4H-imidazole-3-oxide with alkynylmagnesium bromide wereused. The reaction gave corresponding nitroxides with an alkynyl group adjacent to the N-O moiety. The hydrogenation of resulting 2-ethynyl-substituted nitroxides with subsequent re-oxidation of the N-OH group produced the corresponding sterically shielded tetraalkylnitroxides of pyrrolidine, imidazolidine and 2,5-dihydroimidazole series. EPR studies revealed large additional couplings up to 4 G in the spectra of pyrrolidine and imidazolidine nitroxides with substituents in 3- and/or 4-positions of the ring.


Assuntos
Brometos , Imidazolidinas , Óxidos N-Cíclicos/química , Óxidos de Nitrogênio/química , Marcadores de Spin , Óxidos , Pirrolidinas/química , Espectroscopia de Ressonância de Spin Eletrônica/métodos
6.
BMC Neurol ; 22(1): 403, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36324091

RESUMO

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and mild encephalopathy associated with excitotoxicity (MEEX) are the most frequent acute encephalopathies in pediatric patients in Japan. AESD typically presents with biphasic seizures and delayed reduced diffusion in the subcortical area, called bright tree appearance (BTA), on radiological examination. In patients with AESD, arterial spin labeling (ASL) shows decreased cerebral blood flow (CBF) in the hyperacute stage and increased CBF in the acute stage, suggesting the usefulness of ASL for the early diagnosis of AESD. Additionally, proton magnetic resonance spectroscopy (MRS) shows elevated glutamate (Glu) and glutamine (Gln) in AESD. MEEX is a group of mild encephalopathies with transient elevation of Gln on MRS similar to that in AESD; however, MEEX does not include any clinical biphasic course or abnormalities, including BTA on diffusion-weighted imaging. Although the usefulness of ASL for AESD has been reported, there are no reports for patients with MEEX. In this study, we report our experience with a 4-year-old girl diagnosed with MEEX who showed unique findings on ASL. CASE PRESENTATION: The patient was a 4-year-old girl admitted to the emergency room with febrile status epilepticus. Considering the possibility of AESD, vitamin therapy was initiated. ASL-MR imaging (MRI) of the brain performed on the second day showed increased blood flow in the frontal, temporal, and occipital regions with spared central sulcus, which indicated AESD with central sparing. The patient was diagnosed with AESD, and the treatment included pulse steroid therapy and immunoglobulin therapy from day 3. The patient remained mildly unconscious but gradually became conscious by day 7 with no seizures. Brain MRI performed on day 8 did not show any characteristic AESD findings, such as BTA. Furthermore, MRS showed elevated Gln, which, along with the clinical course, led to the diagnosis of MEEX. The patient was discharged on day 16 without obvious sequelae. CONCLUSIONS: ASL may be useful in the early diagnosis of MEEX as well as AESD, facilitating early intervention.


Assuntos
Encefalopatias , Convulsões Febris , Feminino , Humanos , Criança , Lactente , Pré-Escolar , Marcadores de Spin , Encefalopatias/diagnóstico por imagem , Circulação Cerebrovascular , Imagem de Difusão por Ressonância Magnética , Convulsões Febris/diagnóstico , Glutamina
7.
Dis Markers ; 2022: 9204119, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277976

RESUMO

Objective: To study the regional cerebral blood flow (rCBF) in important brain functional areas and the metabolic levels of these brain functional areas in patients with primary hypothyroidism by using arterial spin labeling (ASL) and magnetic resonance spectroscopy (MRS) techniques to explain the possible causes of brain dysfunction in patients with primary hypothyroidism. Methods: Twenty-five patients with primary hypothyroidism (newly diagnosed and not treated) who were treated in the endocrinology department of our hospital were selected as the research group, and 25 healthy patients with normal thyroid function who came to our hospital during the same period with matched gender and age were selected as the control group. ASL and MRS techniques were used to detect and calculate regional cerebral blood flow (rCBF) in the frontal lobe, hippocampus, and posterior cingulate gyrus, as well as N-acetylaspartate/creatine (NAA/Cr), choline/creatine (Cho) in the brain/Cr, and inositol/creatine (mI/Cr) ratio. The correlations between metabolite ratios measured by rCBF, MRS, and serum TSH, FT3, and FT4 levels were analyzed. Results: Compared with the control group, the rCBF in the frontal lobe, hippocampus, and posterior cingulate gyrus of the dominant hemisphere of the hypothyroid patients in the study group decreased significantly (P < 0.05). The comparison of metabolite ratios showed that compared with the control group, the NAA/Cr ratio of the frontal lobe and posterior cingulate gyrus of the study group was significantly decreased, and the Cho/Cr ratio of the posterior cingulate gyrus of the study group was significantly increased. The MI/Cr ratio of the hippocampus was significantly decreased (all P values < 0.05). Correlation analysis showed that rCBF and NAA/Cr in posterior cingulate gyrus were significantly negatively correlated with serum TSH levels (P < 0.05). Conclusion: The changes of rCBF and metabolite ratios in the frontal lobe, hippocampus, and posterior cingulate gyrus of patients with primary hypothyroidism can be detected using ASL and MRS techniques. The changes of rCBF and metabolite ratio and their negative correlation with serum TSH level are helpful to explain the causes of brain dysfunction in patients with primary hypothyroidism.


Assuntos
Creatina , Hipotireoidismo , Humanos , Creatina/metabolismo , Marcadores de Spin , Espectroscopia de Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Colina/metabolismo , Inositol/metabolismo , Hipotireoidismo/diagnóstico por imagem , Hipotireoidismo/metabolismo , Hipotireoidismo/patologia , Tireotropina
8.
Phys Chem Chem Phys ; 24(41): 25214-25226, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36222074

RESUMO

The measurement of distances in proteins can be challenging in the 5-20 Å range, which is outside those accessible through conventional NMR and EPR methods. Recently it was demonstrated that distances in this range could be measured between a nitroxide as a paramagnetic spin label and a nearby fluorine atom (19F) as a nuclear spin label using high-field (W-band/3.4 T) ENDOR spectroscopy. Here we show that such measurements can also be performed using a gadolinium ion (Gd3+) as the paramagnetic tag. Gd3+ has two advantages. (i) A greater electronic spin (S = 7/2) and fast electronic spin-lattice (T1) relaxation, improving sensitivity by allowing data to be collected at lower temperatures. (ii) A narrow EPR signal for the -½ ↔ ½ transition, and therefore no orientation selection artefacts. Signal intensities can be further enhanced by using a trifluoromethyl (C19F3) group instead of a single 19F atom. Using the protein calbindin D9k with a Ca2+ ion replaced by a Gd3+ ion and a trifluoromethylphenylalanine in position 50, we show that distances up to about 10 Å can be readily measured. Longer distances proved more difficult to measure due to variable electronic TM relaxation rates, which lead to broader Lorentzian ENDOR lineshapes. Gd3+ complexes (Gd3+ tags), which reliably display longer TM times, allow longer distances to be measured (8-16 Å). We also provide preliminary evidence that the intensity of ENDOR signals follows the predicted 1/r6 dependence, indicating that distances r > 20 Å can be measured by this method.


Assuntos
Gadolínio , Proteínas , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Marcadores de Spin , Proteínas/química , Gadolínio/química , Espectroscopia de Ressonância Magnética
9.
Biomolecules ; 12(10)2022 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-36291578

RESUMO

Labelling techniques such as electron paramagnetic resonance spectroscopy and single-molecule fluorescence resonance energy transfer, allow access to distances in the range of tens of angstroms, corresponding to the size of proteins and small to medium-sized protein complexes. Such measurements do not require long-range ordering and are therefore applicable to systems with partial disorder. Data from spin-label-based measurements can be processed into distance distributions that provide information about the extent of such disorder. Using such information in modelling presents several challenges, including a small number of restraints, the influence of the label itself on the measured distance and distribution width, and balancing the fitting quality of the long-range restraints with the fitting quality of other restraint subsets. Starting with general considerations about integrative and hybrid structural modelling, this review provides an overview of recent approaches to these problems and identifies where further progress is needed.


Assuntos
Proteínas , Modelos Moleculares , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Marcadores de Spin , Proteínas/química
10.
Sci Rep ; 12(1): 17190, 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36229511

RESUMO

Studying biomolecules in their native environment represents the ideal sample condition for structural biology investigations. Here we present a novel protocol which allows to delivery proteins into eukaryotic cells through a mild thermal stimulation. The data presented herein show the efficacy of this approach for delivering proteins in the intracellular environment of mammalian cells reaching a concentration range suitable for successfully applying biophysical methods, such as double electron electron resonance (DEER) measurements for characterising protein conformations.


Assuntos
Células Eucarióticas , Proteínas , Animais , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Mamíferos , Conformação Proteica , Marcadores de Spin
11.
J Headache Pain ; 23(1): 131, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36195842

RESUMO

BACKGROUND: Migraine aura is a transient, fully reversible visual, sensory, or other central nervous system symptom that classically precedes migraine headache. This study aimed to investigate cerebral blood flow (CBF) alterations of migraine with aura patients (MwA) and without aura patients (MwoA) during inter-ictal periods, using arterial spin labeling (ASL). METHODS: We evaluated 88 migraine patients (32 MwA) and 44 healthy control subjects (HC) who underwent a three-dimensional pseudo-continuous ASL MRI scanning. Voxel-based comparison of normalized CBF was conducted between MwA and MwoA. The relationship between CBF variation and clinical scale assessment was further analyzed. The mean CBF values in brain regions showed significant differences were calculated and considered as imaging features. Based on these features, different machine learning-based models were established to differentiate MwA and MwoA under five-fold cross validation. The predictive ability of the optimal model was further tested in an independent sample of 30 migraine patients (10 MwA). RESULTS: In comparison to MwoA and HC, MwA exhibited higher CBF levels in the bilateral superior frontal gyrus, bilateral postcentral gyrus and cerebellum, and lower CBF levels in the bilateral middle frontal gyrus, thalamus and medioventral occipital cortex (all p values < 0.05). These variations were also significantly correlated with multiple clinical rating scales about headache severity, quality of life and emotion. On basis of these CBF features, the accuracies and areas under curve of the final model in the training and testing samples were 84.3% and 0.872, 83.3% and 0.860 in discriminating patients with and without aura, respectively. CONCLUSION: In this study, CBF abnormalities of MwA were identified in multiple brain regions, which might help better understand migraine-stroke connection mechanisms and may guide patient-specific decision-making.


Assuntos
Epilepsia , Transtornos de Enxaqueca , Enxaqueca com Aura , Enxaqueca sem Aura , Circulação Cerebrovascular/fisiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Enxaqueca com Aura/diagnóstico por imagem , Enxaqueca sem Aura/diagnóstico por imagem , Qualidade de Vida , Marcadores de Spin
12.
J Am Chem Soc ; 144(41): 18896-18907, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36215201

RESUMO

The hydroxyl radical (•OH) is one of the most attractive reactive oxygen species due to its high oxidation power and its clean (photo)(electro)generation from water, leaving no residues and creating new prospects for efficient wastewater treatment and electrosynthesis. Unfortunately, in situ detection of •OH is challenging due to its short lifetime (few ns). Using lifetime-extending spin traps, such as 5,5-dimethyl-1-pyrroline N-oxide (DMPO) to generate the [DMPO-OH]• adduct in combination with electron spin resonance (ESR), allows unambiguous determination of its presence in solution. However, this method is cumbersome and lacks the necessary sensitivity and versatility to explore and quantify •OH generation dynamics at electrode surfaces in real time. Here, we identify that [DMPO-OH]• is redox-active with E0 = 0.85 V vs Ag|AgCl and can be conveniently detected on Au and C ultramicroelectrodes. Using scanning electrochemical microscopy (SECM), a four-electrode technique capable of collecting the freshly generated [DMPO-OH]• from near the electrode surface, we detected its generation in real time from operating electrodes. We also generated images of [DMPO-OH]• production and estimated and compared its generation efficiency at various electrodes (boron-doped diamond, tin oxide, titanium foil, glassy carbon, platinum, and lead oxide). Density functional calculations, ESR measurements, and bulk calibration using the Fenton reaction helped us unambiguously identify [DMPO-OH]• as the source of redox activity. We hope these findings will encourage the rapid, inexpensive, and quantitative detection of •OH for conducting informed explorations of its role in mediated oxidation processes at electrode surfaces for energy, environmental, and synthetic applications.


Assuntos
Radical Hidroxila , Platina , Radical Hidroxila/química , Espécies Reativas de Oxigênio , Microscopia Eletroquímica de Varredura , Titânio , Boro , Óxidos N-Cíclicos/química , Espectroscopia de Ressonância de Spin Eletrônica , Oxirredução , Eletrodos , Água , Carbono , Diamante , Radicais Livres , Marcadores de Spin
13.
Phys Chem Chem Phys ; 24(37): 22645-22660, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36106486

RESUMO

Dipolar electron paramagnetic resonance (EPR) experiments, such as double electron-electron resonance (DEER), measure distributions of nanometer-scale distances between unpaired electrons, which provide valuable information for structural characterization of proteins and other macromolecular systems. We present an extension to our previously published general model based on dipolar pathways valid for multi-dimensional dipolar EPR experiments with more than two spin-1/2 labels. We examine the 4-pulse DEER and TRIER experiments in terms of dipolar pathways and show experimental results confirming the theoretical predictions. This extension to the dipolar pathways model allows the analysis of previously challenging datasets and the extraction of multivariate distance distributions.


Assuntos
Proteínas , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Substâncias Macromoleculares , Proteínas/química , Marcadores de Spin
14.
J Cereb Blood Flow Metab ; 42(12): 2188-2190, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36113055

RESUMO

This study evaluated the association between systemic arterial blood pressure and cerebral perfusion in 740 participants of the UK's largest tri-ethnic study with measurements of cerebral blood flow (CBF) performed using arterial spin labelling MRI. A significant negative correlation between blood pressure, age and CBF was observed across the patient cohort. The lowest CBF values were recorded in the group of patients with hypertension that were prescribed with anti-hypertensive drugs, but uncontrolled on medication. These findings confirm that hypertension is associated with reduced cerebral perfusion and highlight the importance of blood pressure control for the benefit of maintaining brain blood flow.


Assuntos
Circulação Cerebrovascular , Hipertensão , Humanos , Circulação Cerebrovascular/fisiologia , Perfusão , Hipertensão/tratamento farmacológico , Imageamento por Ressonância Magnética , Pressão Sanguínea , Marcadores de Spin
15.
ACS Chem Biol ; 17(9): 2448-2460, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36069699

RESUMO

Pulsed electron-electron double resonance (PELDOR) spectroscopy, X-ray scattering interferometry (XSI), and single-molecule Förster resonance energy transfer (smFRET) are molecular rulers that provide inter- or intramolecular pair-wise distance distributions in the nanometer range, thus being ideally suitable for structural and dynamic studies of biomolecules including RNAs. The prerequisite for such applications requires site-specific labeling of biomolecules with spin labels, gold nanoparticles, and fluorescent tags, respectively. Recently, site-specific labeling of large RNAs has been achieved by a combination of transcription of an expanded genetic alphabet containing A-T/G-C base pairs and NaM-TPT3 unnatural base pair (UBP) with post-transcriptional modifications at UBP bases by click chemistry or amine-NHS ester reactions. However, due to the bulky sizes of functional groups or labeling probes used, such strategies might cause structural perturbation and decrease the accuracy of distance measurements. Here, we synthesize an α-thiophosphorylated variant of rTPT3TP (rTPT3αS), which allows for post-transcriptional site-specific labeling of large RNAs at the internal α-phosphate backbone via maleimide-modified probes. Subsequent PELDOR, XSI, and smFRET measurements result in narrower distance distributions than labeling at the TPT3 base. The presented strategy provides a new route to empower the molecular rulers for structural and dynamic studies of large RNA and its complex.


Assuntos
Ouro , Nanopartículas Metálicas , Aminas , Espectroscopia de Ressonância de Spin Eletrônica , Ésteres , Ouro/química , Maleimidas , Fosfatos , RNA , Marcadores de Spin
16.
Methods Mol Biol ; 2548: 83-96, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36151493

RESUMO

Site-directed spin labeling EPR (electron paramagnetic resonance) spectroscopy is a technique used to identify the local conformational changes at a specific residue of interest within a purified protein in response to a ligand. Here, we describe the site-directed spin labeling EPR spectroscopy methodology to monitor changes in the side-chain motion in soluble lipopolysaccharide transport proteins upon the addition of lipopolysaccharide (LPS). A comparison of the spectral overlays of the spin-labeled protein in the absence and presence of LPS provides a qualitative visualization of how LPS binding affects the motion of each spin-labeled site tested within the protein. No change in the spectral lineshapes of a spin-labeled protein in the absence and presence of LPS indicates that the site is not affected by LPS binding, while differences in the spectral lineshapes indicate that LPS does affect the mobility of the spin label side chain within the protein structure. This is a powerful readout of conformational changes at specific residues of interest that can be used to identify a specific site as a reporter of changes induced by ligand binding and to map out the effects of ligand binding through an array of reporter sites within a protein. With the use of AquaStar tubing, protein concentrations as low as 2 µM allow for up to a 100-fold excess of LPS. This methodology may also be applied to other protein-ligand or protein-protein interactions with minor adaptations.


Assuntos
Proteínas de Transporte , Lipopolissacarídeos , Proteínas de Transporte/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Ligantes , Lipopolissacarídeos/química , Proteínas/metabolismo , Marcadores de Spin
17.
J Am Chem Soc ; 144(39): 17841-17847, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36125359

RESUMO

Understanding thermal phase behavior within nanomaterials can inform their rational design for medical technologies like drug delivery systems and vaccines, as well as for energy technologies and catalysis. This study resolves thermal phases of discrete domains within a supramolecular aramid amphiphile (AA) nanoribbon. Dynamics are characterized by X-band EPR spectroscopy of spin labels positioned at specific sites through the nanoribbon cross-section. The fitting of the electron paramagnetic resonance (EPR) line shapes reveals distinct conformational dynamics, with fastest dynamics at the surface water layer, intermediate dynamics within the flexible cationic head group domain, and slowest dynamics in the interior aramid domain. Measurement of conformational mobility as a function of temperature reveals first- and second-order phase transitions, with melting transitions observed in the surface and head group domains and a temperature-insensitive crystalline phase in the aramid domain. Arrhenius analysis yields activation energies of diffusion at each site. This work demonstrates that distinct thermal phase behaviors between adjacent nanodomains within a supramolecular nanostructure may be resolved and illustrates the utility of EPR spectroscopy for thermal phase characterization of nanostructures.


Assuntos
Nanotubos de Carbono , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Conformação Molecular , Marcadores de Spin , Água/química
18.
Acta Neurol Scand ; 146(5): 635-642, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36062837

RESUMO

BACKGROUND: Robust collateral circulation is strongly associated with good outcomes in acute ischemic stroke (AIS). AIMS: To determine whether collateral circulation detected by arterial spin labeling (ASL) magnetic resonance imaging could predict good clinical outcome in AIS patients with 90 days follow-up. MATERIALS AND METHODS: Total 58 AIS patients with anterior circulation stroke were recruited. Collateral circulation was defined as arterial transit artifact in ASL images. Modified Rankin Scale (mRS), the Barthel Index, and National Institutes of Health Stroke Scale (NIHSS) were employed to evaluate neurological function for the baseline and 90 days follow-up. The percent changes of these scores were also calculated, respectively. Finally, a support vector classifier model of machine learning and receiver operating characteristic curve were employed to estimate the power of ASL collaterals (ASLcs) predicting the clinical outcome. RESULTS: Patients with ASLcs represented higher rate of good outcome (83.30% vs. 31.25%, p < .001) and lower follow-up mRS scores (p < .001), when compared to patients without ASLcs. There were significant differences for percent changes of mRS scores and NIHSS scores between these two groups. Further, the presence of ASLcs could predict good clinical outcome (OR, 1.54; 95% CI, 1.10-2.16), even after controlling for baseline NIHSS scores. The SVC model incorporating baseline NIHSS scores and ASLcs had significant predictive effect (accuracy, 79.3%; AUC, 0.806) on clinical prognosis for AIS patients. DISCUSSION: We targeted on the non-invasive assessment of collateral circulation using ASL technique and found that patients with ASLcs were more likely to have a good clinical outcome after AIS. This finding is of guiding significance for treatment selection and prognostic prediction. CONCLUSIONS: Early ASLcs assessment provides a good powerful tool to predict clinical outcome for AIS patients with 90 days follow-up.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Circulação Cerebrovascular , Circulação Colateral , Humanos , AVC Isquêmico/diagnóstico por imagem , Estudos Retrospectivos , Marcadores de Spin , Acidente Vascular Cerebral/complicações , Resultado do Tratamento
19.
Sci Data ; 9(1): 543, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068231

RESUMO

Arterial spin labeling (ASL) is a non-invasive MRI technique that allows for quantitative measurement of cerebral perfusion. Incomplete or inaccurate reporting of acquisition parameters complicates quantification, analysis, and sharing of ASL data, particularly for studies across multiple sites, platforms, and ASL methods. There is a strong need for standardization of ASL data storage, including acquisition metadata. Recently, ASL-BIDS, the BIDS extension for ASL, was developed and released in BIDS 1.5.0. This manuscript provides an overview of the development and design choices of this first ASL-BIDS extension, which is mainly aimed at clinical ASL applications. Discussed are the structure of the ASL data, focussing on storage order of the ASL time series and implementation of calibration approaches, unit scaling, ASL-related BIDS fields, and storage of the labeling plane information. Additionally, an overview of ASL-BIDS compatible conversion and ASL analysis software and ASL example datasets in BIDS format is provided. We anticipate that large-scale adoption of ASL-BIDS will improve the reproducibility of ASL research.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Neuroimagem , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/análogos & derivados , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/normas , Neuroimagem/métodos , Reprodutibilidade dos Testes , Marcadores de Spin
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(8): 1016-1024, 2022 Aug 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36097769

RESUMO

OBJECTIVES: The patients with mild traumatic brain injury (mTBI) accounts for more than 80% of the patients with brain injury. Most patients with mTBI have no abnormalities in CT examination. Therefore, most patients choose to self-care and recover rather than seeking medical treatment. In fact, mTBI may result in persistent cognitive decline and neurobehavioral dysfunction. In addition, changes occurred in neurochemistry, metabolism, and cells after injury may cause changes in cerebral blood flow (CBF), which is one of the causes of secondary injury and slow brain repair. This study aims to evaluate the changes of CBF with the progression of the disease in patients with mTBI based on arterial spin labeling (ASL) magnetic resonance imaging technology. METHODS: In the outpatient or emergency department of the Second Affiliated Hospital of Wenzhou Medical University, 43 mTBI patients were collected as an mTBI group, and 43 normal subjects with age, gender, and education level matching served as a control group. They all received clinical neuropsychology and cognitive function evaluation and magnetic resonance imaging. In the mTBI group, 22 subjects were followed up at acute phase, 1 month, 3 months, and 12 months. Based on the control group, the abnormal regions of CBF in the whole brain of mTBI patients were analyzed. The abnormal regions were taken as the regions of interest (ROI). The correlation of the values of the CBF in ROIs with clinical indications, cognitive function, and the changes of CBF in ROI at each time point during the follow-up were analyzed. RESULTS: Compared with the control group, the CBF in the bilateral dorsolateral superior frontal gyrus and auxiliary motor areas in the cortical region, as well as the right putamen, caudate nucleus, globus pallidus, and parahippocampus in the subcutaneous regions in the acute phase of the mTBI group were significantly increased (all P<0.01, TFCE-FWE correction). The analysis results of correlation of CBF with neuropsychology and cognitive domain showed that in the mTBI group, whole brain (r=0.528, P<0.001), right caudate nucleus (r=0.512, P<0.001), putamen (r=0.486, P<0.001), and globus pallidus (r=0.426, P=0.006) values of the were positively correlated with Backward Digit Span Test (BDST) score (reflectting working memory ability), and the right globus pallidus CBF was negatively correlated with the Post-Traumatic Stress Disorder Cheeklist-CivilianVersion (PCL-C) score (r=-0.402, P=0.010). Moreover, the follow-up study showed that abnormal CBF in these areas had not been restored. The correlation of CBF was negatively correlated with PCL-C and BDST at 1 months, 3 months, and 12 months (all P>0.05). CONCLUSIONS: The elevated CBF value is one of the stress characteristics of brain injury in the mTBI patients at the acute phase. There is abnormal elevation of CBF values in multiple cortex or subcortical areas. Multi-time point studies show that there is no obvious change of CBF in abnormal areas, suggesting that potential clinical treatment is urgently needed for the mTBI patients.


Assuntos
Concussão Encefálica , Lesões Encefálicas , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Marcadores de Spin
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