Application of N-methyl-D-aspartate receptor nanopore in screening ligand molecules.

N-methyl-D-aspartate receptors (NMDARs) are crucial for excitatory synaptic transmission in the central nervous system. To study NMDARs more accurately and conveniently, we developed a stable NMDAR nanopore in a planar lipid bilayer. Pharmacological properties were validated using the allosteric modulator Ro 25-6981 and antagonist D-2-amino-5-phosphonopentanoic acid (D-APV). The cyanotoxin ß-N-methylamino-L-alanine (BMAA) found in fresh water systems is suspected to be associated with the development of neurodegenerative diseases. Therefore, BMAA and its two isomers L-2, 4-Diaminobutyric acid dihydrochloride (DAB) and N-(2-aminoethyl) glycine (AEG) and an endogenous excitotoxin, quinolinic acid (QA), were studied using the NMDAR nanopores to assess their effects on NMDAR modulation. We demonstrated that the NMDAR nanopore could reliably detect its ligand molecules at the single-channel level. The study also demonstrated the practicability of NMDAR nanopores, and results were validated using two-electrode voltage-clamp (TEVC) recording. Compared with TEVC recording, the NMDAR nanopores conducted ion channel gating at the single-channel level without being affected by other proteins on the cell membrane. The highly sensitive and accurate NMDAR nanopore technique thus has a unique advantage in screening NMDAR ligand molecules that could be associated with neurodegenerative disease.

Reversible switching of a supramolecular morphology driven by an amphiphilic bistable [2]rotaxane.

An acid/base responsive amphiphilic [2]rotaxane switch containing a hydrophilic macrocycle component and a hydrophobic terminal bulky group was prepared and characterized. The morphology of the supramolecular assemblies formed by the rotaxanes could be switched between spherical vesicles and worm-like micelles using acid/base stimuli, as confirmed by transmission electron microscopy (TEM).

Quantitative iodine-based material decomposition images with spectral CT imaging for differentiating prostatic carcinoma from benign prostatic hyperplasia.

RATIONALE AND OBJECTIVES: To investigate the value of iodine-based material decomposition images produced via spectral computed tomography (CT) in differentiating prostate cancer (PCa) from benign prostate hyperplasia (BPH). MATERIALS AND METHODS: Fifty-six male patients underwent CT examination with spectral imaging during arterial phase (AP), venous phase (VP), and parenchymal phase (PP) of enhancement. Iodine concentrations of lesions were measured and normalized to that of the obturator internus muscle. Lesion CT values at 75 keV (corresponding to the energy of polychromatic images at 120 kVp) were measured and also normalized; their differences between AP and VP, VP and PP, and PP and AP were also obtained. The two-sample t-test was performed for comparisons. A receiver operating characteristic curve was generated to establish the threshold for normalized iodine concentration (NIC). RESULTS: Fifty-two peripheral lesions were found, which were confirmed by biopsy as 28 cases of PCa and 24 BPHs. The NICs of prostate cancers significantly differed from those of the BPHs: 2.38 ± 1.72 compared with 1.21 ± 0.72 in AP, respectively, and 2.67 ± 0.61 compared with 2.27 ± 0.77 in VP. Receiver operating characteristic analysis indicated that an NIC of 1.24 in the AP provided a sensitivity of 88% and a specificity of 71% for differentiating PCa from BPH. CONCLUSIONS: Spectral CT imaging enabled quantitative depiction of contrast medium uptake in prostatic lesions and improved sensitivity and specificity for differentiating PCa from BPH.

Counterion-induced changes to the micellization of surfactin-C16 aqueous solution.

The effects of counterions on surfactin-C(16) micelle solution with its critical micelle concentration (cmc), microenvironment properties in micelles, micelle size distribution, and morphology were investigated by fluorescence, dynamic light-scattering, and freeze-fracture transmission electron microscopy measurements. Counterions enhanced the surface activity of surfactin-C(16) and reduced the cmc. With the micellization of surfactin-C(16), it adopted a beta-sheet conformation, and univalent concentrations reduced micelle micropolarity, increased micelle microviscosity, and tended to cause formation of small and spherical micelles, while divalent counterions had a special effect. With low concentration of divalent cations, they had strong interaction with surfactin-C(16) micelles and tended to form larger micelle aggregates.