Search

Though distinct pathological entities, corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) share multiple biochemical and genetic features suggesting overlapping pathophysiolog...

Purpose EEG is a common diagnostic tool to localize epileptic activity with excellent temporal resolution and, however, with relatively low spatial resolution. High-density EEG recording is limited in clinical practice, mainly because of electrode placement difficulties, need of high technical skills, and advanced equipment requirement. Methods We described the technique of long-term EEG recording using a 128-channel neoprene cap placed with a dielectric paste in 7 patients with refractory epilepsy. We captured electrographic seizures in six of seven patients. The 128-channel EEG cap was well tolerated except for a mild headache. Daily impedance checks and reapplication of the high impedance leads maintained the recording with impedances below 10 kΩ. Results Successful long-term recording of high-density EEG was able to capture seizures in six of seven patients. The time needed to apply the electrodes was approximately 1 hour and approximately 30 minutes daily for maintenance. The EEG source localization was obtained in six of seven patients, concordant within the sublobar region for both standard and high-density EEG recordings. Three patients reported a mild headache not leading to discontinuation of the recording. Conclusions In general, long-term high-density scalp EEG recording with a dielectric paste is well tolerated and allows capturing both interictal and ictal data for localization. This small sample does not show a significant advantage in terms of sublobar localization when high-density EEG source is compared with standard 10 to 20 placement as long as the subtemporal areas are recorded.

The Spike protein of SARS-CoV2 and other coronaviruses mediate host cell entry and are S-acylated on multiple phylogenetically conserved cysteine residues. Multiple protein acyltransferase enzymes of the ZDHHC family have been reported to modify Spike proteins post-translationally. Using resin-assisted capture mass spectrometry, we demonstrate that the Spike protein is S-acylated in SARS-CoV2 infected human and monkey cells. We further show that increased abundance of the human acyltransferase ZDHHC5 results in increased S-acylation of the SARS-CoV2 Spike protein, whereas ZDHHC5 knockout cells had a 40% reduction in the incorporation of an alkynyl-palmitate using click chemistry detection. We also find that the S-acylation of the Spike protein is not limited to palmitate, as clickable versions of myristate and stearate were also found on the immunocaptured protein. Yet, ZDHHC5 was highly selective for palmitate, suggesting that other ZDHHC enzymes mediated the incorporation of other fatty acyl chains. Thus, since multiple ZDHHC isoforms may modify the Spike protein, we examined the ability of the fatty acid synthase inhibitor TVB-3166 to prevent the S-acylation of the Spike proteins of SARS-CoV-2 and human CoV-229E. Treating cells with TVB-3166 inhibited S-acylation of ectopically expressed SARS-CoV2 Spike and attenuated the ability of SARS-CoV2 and human CoV-229E to spread in vitro. Additionally, treatment of mice with a comparatively low dose of TVB-3166 promoted survival from an otherwise fatal murine coronavirus infection. Our findings further substantiate the necessity of CoV Spike protein S-acylation and the potential use of fatty acid synthase inhibitors.

To meet the urgent demand for better diagnostic tools to combat the ongoing COVID-19 pandemic, we developed a homogeneous immunoassay to detect IgG antibodies against SARS-CoV-2. This assay is based on a tri-part Nanoluciferase (tNLuc) approach, in which the spike protein of SARS-CoV-2 and protein G, fused respectively to two different tNLuc tags, are used as antibody probes. Target engagement of the probes allows reconstitution of a functional luciferase in the presence of the third tNLuc component. The assay is performed directly in liquid phase of patient sera and enables rapid, quantitative and low-cost detection. We show that tNLuc maintains a similar sensitivity to ELISA, while its readouts are highly consistent with various neutralizing antibody assays. This proof-of-principle study suggests potential applications in diagnostics and disease and vaccination management.

The diagnosis of atypical paroxysmal events represents a significant challenge for clinicians when differentiating epileptic from nonepileptic events. The ictal manifestations of pharyngeal dysesthesias are often misdiagnosed and difficult to distinguish clinically, given their subtle features such as pharyngeal discomfort with and without autonomic symptomology. We report a rare case of isolated ictal pharyngeal dysesthesias localizing to the non-dominant frontal operculum lobe misdiagnosed as psychogenic and later confirmed by continuous video-EEG monitoring.

As ictal semiology is increasingly understood to arise from epileptogenic networks, high-frequency oscillation propagation patterns are helping elucidate networks relevant for surgical planning. Musical automatisms, a well-documented but very rare phenomenon of epilepsy, have yet to be examined as a manifestation of high-frequency propagation in the public literature. In our current study, we report a rare case intractable epilepsy with ictal humming whose epileptogenic zone was associated with the non-dominant left anterior medial temporal region. Mapping our case's ictal semiology and high-frequency propagation pattern both facilitated treatment and further supports prior observations that the rare phenomena of musical automatisms localize to a non-dominant frontal-temporal network rather than a specific cortical territory.

The human recombinant S-Lac lectin, L-14-II, produced in an Escherichia coli expression system, has been co-crystallized in the presence of lactose by the hanging drop vapor diffusion method. The crystals grow in space group P2(1)2(1)2(1) with unit cell dimensions of a = 43.6 A, b = 57.8 A, c = 108.2 A, with a dimer in the asymmetric unit. On a conventional rotating anode the crystals diffract to at least 2.8 A resolution.