Misfolded α-synuclein amyloid fibrils are the principal components of Lewy bodies and neurites, hallmarks of Parkinson’s disease (PD). Here we present a high-resolution structure of an α-synuclein fibril, in a form that induces robust pathology in primary neuronal culture, determined by solid-state NMR spectroscopy and validated by electron microscopy and X-ray fiber diffraction. Over 200 unique long-range distance restraints define a consensus structure with common amyloid features including parallel in-register β-sheets and hydrophobic core residues, but also substantial complexity, arising from diverse structural features: an intermolecular salt bridge, a glutamine ladder, close backbone interactions involving small residues, and several steric zippers stabilizing a novel, orthogonal Greek-key topology. These characteristics contribute to the robust propagation of this fibril form, as evidenced by structural similarity of early-onset PD mutants. The structure provides a framework for understanding the interactions of α-synuclein with other proteins and small molecules to diagnose and treat PD.

By using simple modifications to standard MR imaging sequences, diagnostic-quality MR imaging of THA complications can be performed, particularly around the femoral prosthetic stem.

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Nine patients with initial magnetic resonance (MR) imaging and clinical findings suggestive of spinal dural arteriovenous fistula (AVF) underwent spinal MR angiography with an autotriggered elliptic centric ordered three-dimensional gadolinium-enhanced technique (hereafter, this MR angiographic technique) before conventional intraarterial angiography. In all nine patients, findings with this MR angiographic technique correctly and precisely localized the spinal dural AVF. Observer error resulted in one case in which the site of the fistula was not prospectively reported but was easily identified retrospectively on the spinal MR angiogram.

The MYB-bHLH-WDR (MBW) complex activates anthocyanin biosynthesis through the transcriptional regulation. RsMYB1 has been identified as a key player in anthocyanin biosynthesis in red radish (Raphanus sativus L.), but its partner bHLH transcription factor (TF) remains to be determined. In this study, we isolated a bHLH TF gene from red radish. Phylogenetic analysis indicated that this gene belongs to the TT8 clade of the IIIF subgroup of bHLH TFs, and we thus designated this gene RsTT8. Subcellular localization analysis showed that RsTT8-sGFP was localized to the nuclei of Arabidopsis thaliana protoplasts harboring the RsTT8-sGFP construct. We evaluated anthocyanin biosynthesis and RsTT8 expression levels in three radish varieties (N, C, and D) that display different red phenotypes in the leaves, root flesh, and root skins. The root flesh of the C variety and the leaves and skins of the D variety exhibit intense red pigmentation; in these tissues, RsTT8 expression showed totally positive association with the expression of RsMYB1 TF and of five of eight tested anthocyanin biosynthesis genes (i.e., RsCHS, RsCHI, RsF3H, RsDFR, and RsANS). Heterologous co-expression of both RsTT8 and RsMYB1 in tobacco leaves dramatically increased the expression of endogenous anthocyanin biosynthesis genes and anthocyanin accumulation. Furthermore, a yeast two-hybrid assay showed that RsTT8 interacts with RsMYB1 at the MYB-interacting region (MIR), and a transient transactivation assay indicated that RsTT8 activates the RsCHS and RsDFR promoters when co-expressed with RsMYB1. Complementation of the Arabidopsis tt8-1 mutant, which lacks red pigmentation in the leaves and seeds, with RsTT8 restored red pigmentation, and resulted in high anthocyanin and proanthocyanidin contents in the leaves and seeds, respectively. Together, these results show that RsTT8 functions as a regulatory partner with RsMYB1 during anthocyanin biosynthesis.

Auto-triggered elliptic centric-ordered three-dimensional (3D) gadolinium-enhanced magnetic resonance (MR) angiography was compared with 3D multiple overlapping thin-slab acquisition time-of-flight (TOF) MR angiography in the evaluation of intracranial arteriovenous malformations (AVMs) in 10 patients. Intraarterial digital subtraction angiography (DSA) was the reference standard. Gadolinium-enhanced MR angiograms were found to be equivalent to DSA images in AVM component depiction in 70%--90% of cases and were consistently superior to TOF MR angiograms.

SummaryWe investigated the short-and long-term effects of ceftriaxone on GLT-1 transporter activity and extracellular glutamate in the rat nucleus accumbens. Repeated ceftriaxone administration (50, 100 or 200 mg/kg, i.p.) produced a dose-dependent reduction in glutamate levels that persisted for 20 days following discontinuation of drug exposure. The ceftriaxone effect was prevented bythe GLT-1 transporter inhibitor dihydrokainate (DHK) (1 μM, intra-accumbal). These results suggest β-lactam antibiotics produce an enduring reduction in glutamatergic transmission in the brain reward center.

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