Fractional deuteration applied to biomolecular solid-state NMR spectroscopy

Solid-state Nuclear Magnetic Resonance can provide detailed insight into structural and dynamical aspects of complex biomolecules. With increasing molecular size, advanced approaches for spectral simplification and the detection of medium to long-range contacts become of critical relevance. We have analyzed the protonation pattern of a membrane-embedded ion channel that was obtained from bacterial expression using protonated precursors and D2O medium. We find an overall reduction of 50% in protein protonation. High levels of deuteration at Hα and Hβ positions reduce spectral congestion in (1H,13C,15N) correlation experiments and generate a transfer profile in longitudinal mixing schemes that can be tuned to specific resonance frequencies. At the same time, residual protons are predominantly found at amino-acid side-chain positions enhancing the prospects for obtaining side-chain resonance assignments and for detecting medium to long-range contacts. Fractional deuteration thus provides a powerful means to aid the structural analysis of complex biomolecules by solid-state NMR

Onyx embolization of skull base paragangliomas: a single-center experience.

BACKGROUND: Skull base paragangliomas are highly vascular tumors that are often embolized before surgical resection; however, the safety and efficacy of preoperative embolization using an ethylene vinyl alcohol copolymer (Onyx; Medtronic, Dublin, Republic of Ireland) in these tumors is unknown. This retrospective cohort study evaluated patient outcomes after preoperative embolization of skull base paragangliomas using Onyx. METHODS: We retrospectively analyzed data from all patients with skull base paragangliomas who underwent preoperative Onyx embolization at our institution (January 01, 2005-December 31, 2017). Patient, tumor, embolization, and outcomes data were extracted by reviewing inpatient and outpatient clinical and imaging records. RESULTS: Seven patients were studied (5/7 [71%] female), 6 with glomus jugulares and 1 with a glomus vagale. The median age was 52 years, and the most common presenting symptom was cranial neuropathy (6/7 [86%]). The tumor vascular supply was from the ascending pharyngeal artery in all 7 cases (100%) with additional feeders including the occipital artery in 5 (71%); internal carotid artery in 3 (43%); middle meningeal, vertebral, and internal maxillary artery each in 2 (29%); and posterior auricular artery in 1 (14%). The median postembolization tumor devascularization was 80% (range, 64-95%). The only postembolization complication was a facial palsy in 1 patient. CONCLUSION: Preoperative embolization with Onyx affords excellent devascularization for the majority of skull base paragangliomas, and it may facilitate resection of these hypervascular lesions. The advantages provided by Onyx with respect to penetration of intratumoral vessels must be weighed against the risk of cranial neuropathy

Locked-in Intact Functional Networks in Children with Autism Spectrum Disorder: A Case-Control Study

Resting-state functional magnetic resonance imaging (rs-fMRI) has the potential to investigate abnormalities in brain network structure and connectivity on an individual level in neurodevelopmental disorders, such as autism spectrum disorder (ASD), paving the way toward using this technology for a personalized, precision medicine approach to diagnosis and treatment. Using a case-control design, we compared five patients with severe regressive-type ASD to five patients with temporal lobe epilepsy (TLE) to examine the association between brain network characteristics and diagnosis. All children with ASD and TLE demonstrated intact motor, language, and frontoparietal (FP) networks. However, aberrant networks not usually seen in the typical brain were also found. These aberrant networks were located in the motor (40%), language (80%), and FP (100%) regions in children with ASD, while children with TLE only presented with aberrant networks in the motor (40%) and language (20%) regions, in addition to identified seizure onset zones. Fisher’s exact test indicated a significant relationship between aberrant FP networks and diagnosis (p = 0.008), with ASD and atypical FP networks co-occurring more frequently than expected by chance. Despite severe cognitive delays, children with regressive-type ASD may demonstrate intact typical cortical network activation despite an inability to use these cognitive facilities. The functions of these intact cognitive networks may not be fully expressed, potentially because aberrant networks interfere with their long-range signaling, thus creating a unique “locked-in network” syndrome