Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection. 相似文献
Nano Research - Development of colored surfaces by formation of nano-structured aggregates is a widely used strategy in nature to color lightweight structures (e.g. butterflies) without the use of... 相似文献
To develop a 3D multi-contrast IVW protocol with 0.5-mm isotropic resolution and a scan time of 5 min per sequence.
Materials and methods
Pre-contrast T1w VISTA, DANTE prepared PDw VISTA, SNAP, and post-contrast T1w VISTA were accelerated using cartesian undersampling with target ordering method (CUSTOM) and self-supporting tailored k-space estimation for parallel imaging reconstruction (STEP). CUSTOM + STEP IVW was compared to full-sample IVW, SENSE-accelerated IVW, and CUSTOM + zero-filled Fourier reconstruction in normal volunteers and subjects with intracranial atherosclerotic disease (ICAD). Image quality, vessel delineation, CSF suppression, and blood suppression were compared.
Results
CUSTOM + STEP vessel wall delineation was comparable to full-sample IVW and better than SENSE IVW for vessel wall delineation on T1w VISTA and luminal contrast on SNAP. Average image quality and wall depiction were significantly improved using STEP reconstruction compared with zero-filled Fourier reconstruction, with no significant difference in CSF or blood suppression.
Conclusions
CUSTOM + STEP allowed multi-contrast 3D 0.5-mm isotropic IVW within 30 min. Although some quantitative and qualitative scores for CUSTOM − STEP were lower than fully sampled IVW, CUSTOM + STEP provided comparable vessel wall delineation as full-sample IVW and was superior to SENSE. CUSTOM + STEP IVW was well tolerated by patients and showed good delineation of ICAD plaque.
Migraine is a common neurological disease that affects about 11% of the adult population. The disease is divided into two main clinical subtypes: migraine with aura and migraine without aura. According to the neurovascular theory of migraine, the activation of the trigeminovascular system (TGVS) and the release of numerous neuropeptides, including calcitonin gene-related peptide (CGRP) are involved in headache pathogenesis. TGVS can be activated by cortical spreading depression (CSD), a phenomenon responsible for the aura. The mechanism of CSD, stemming in part from aberrant interactions between neurons and glia have been studied in models of familial hemiplegic migraine (FHM), a rare monogenic form of migraine with aura. The present review focuses on those interactions, especially as seen in FHM type 1, a variant of the disease caused by a mutation in CACNA1A, which encodes the α1A subunit of the P/Q-type voltage-gated calcium channel. 相似文献
The current research work presents a facile and cost–effective co-precipitation method to prepare doped (Co & Fe) CuO and undoped CuO nanostructures without usage of any type of surfactant or capping agents. The structural analysis reveals monoclinic crystal structure of synthesized pure CuO and doped-CuO nanostructures. The effect of different morphologies on the performance of supercapacitors has been found in CV (cyclic voltammetry) and GCD (galvanic charge discharge) investigations. The specific capacitances have been obtained 156 (±5) Fg?1, 168(±5) Fg?1 and 186 (±5) Fg?1 for CuO, Co-doped CuO and Fe-doped CuO electrodes, respectively at scan rate of 5 mVs?1, while it is found to be 114 (±5) Fg?1, 136 (±5) Fg?1 and 170 (±5) Fg?1 for CuO, Co–CuO and Fe–CuO, respectively at 0.5 Ag-1 as calculated from the GCD. The super capacitive performance of the Fe–CuO nanorods is mainly attributed to the synergism that evolves between CuO and Fe metal ion. The Fe-doped CuO with its nanorods like morphology provides superior specific capacitance value and excellent cyclic stability among all studied nanostructured electrodes. Consequently, it motivates to the use of Fe-doped CuO nanostructures as electrode material in the next generation energy storage devices. 相似文献
For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABAA receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis. 相似文献
While qualitative studies have identified chlorogenic acids in antioxidant extracts, particularly ethyl acetate‐derived extracts, of Taraxacum officinale, quantitative analysis of these phenolic compounds remains largely unreported for this species. In this study, bioactivity‐guided fractionation of an antioxidant crude ethyl acetate extract (DPPH = 295.481 ± 0.955 mg TE g?1 extract) from T. officinale root resulted in a number of reverse‐phase fractions that demonstrated high antioxidant activity (DPPH = 1058.733–1312.136 mg TE g?1 extract), stronger than that of the synthetic antioxidant Trolox®. UPLC‐MS/MS screening of these fractions for the presence of selected mono‐ and di‐caffeoylquinic acids revealed large quantities of 1,5‐dicaffeoylquinic acid present in several fractions (853.052–907.324 μg mg?1), respectively. Due to the antioxidant potency and high levels of 1,5‐dicaffeoylquinic acid observed in these fractions, it was concluded that specifically this chlorogenic acid derivative is a major contributor to the antioxidant efficacy of dandelion root. 相似文献
We study magnetic-field directed self-assembly of magnetic nanoparticles onto templates recorded on perpendicular magnetic recording media, and quantify feature width and height as a function of assembly time. Feature widths are determined from Scanning Electron Microscope (SEM) images, while heights are obtained with Atomic Force Microscopy (AFM). For short assembly times, widths were ~150 nm, while heights were ~14 nm, a single nanoparticle on average with a 10:1 aspect ratio. For long assembly times, widths approach 550 nm, while the average height grows to 3 nanoparticles, ~35 nm; a 16:1 aspect ratio. We perform magnetometry on these self-assembled structures and observe the slope of the magnetic moment vs. field curve increases with time. This increase suggests magnetic nanoparticle interactions evolve from nanoparticle–nanoparticle interactions to cluster–cluster interactions as opposed to feature–feature interactions. We suggest the aspect ratio increase occurs because the magnetic field gradients are strongest near the transitions between recorded regions in perpendicular media. If these gradients can be optimized for assembly, strong potential exists for using perpendicular recording templates to assemble complex heterogeneous materials. 相似文献