Project description:Holmes tremor is a rare kind of hyperkinetic movement disorder, clinically characterized by irregular, monolateral, high-amplitude jerks, sharing a quite similar frequency with those observed in Parkinson's disease; its generation likely relies on a combined involvement of cerebello-thalamic and nigrostriatal pathways.We report the case of a man with a combined resting-postural-kinetic tremor. Neuroimaging revealed an intracranial dermoid cyst at the right pontocerebellar angle with brainstem dislocation. We performed an extensive electrophysiological assessment from the extensor digitorum communis (EDC) and flexor carpi radialis (FCR) muscles.Both the spontaneous variability of tremor frequency and frequency entrainment argued against an organic aetiology. Polymyography revealed: 1) a paradoxical increase of tremor amplitude with mass loading; 2) jerks' synchronization between antagonistic muscles during voluntary contralateral motor performances; 3) tremor inhibition while asking the patient to make a ballistic movement.We suggest a complete psychogenic genesis or, at least in part, a possible co-existence of a rubral tremor with functional traits.Here, we propose a simple and fast test battery for an early diagnosis of functional tremor. Our results prompt further studies to re-define electrodiagnostic criteria in hyperkinetic movement disorders, possibly updating the floating border between organic and psychogenic disease.
Project description:Studies have indicated that the intracellular nicotinamide adenine dinucleotide (NAD+) level is associated with the occurrence and development of many diseases. However, traditional nicotinamide adenine dinucleotide (NAD+) detection techniques are time-consuming and may require large and expensive instruments. We recently found that the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a protein can be inactivated by AcrVA5-mediated acetylation and reactivated by CobB, using NAD+ as the co-factor. Therefore, in this study, we created a CRISPR-Cas12a-based one-step HOLMES(NAD+) system for rapid and convenient NAD+ detection with the employment of both acetylated Cas12a and CobB. In HOLMES(NAD+), acetylated Cas12a loses its trans-cleavage activities and can be reactivated by CobB in the presence of NAD+, cutting ssDNA reporters to generate fluorescence signals. HOLMES(NAD+) shows both sensitivity and specificity in NAD+ detection and can be used for quantitative determination of intracellular NAD+ concentrations. Therefore, HOLMES(NAD+) not only provides a convenient and rapid approach for target NAD+ quantitation but also expands the application scenarios of HOLMES to non-nucleic acid detection.