Objective: Essential Tremor (ET) is one of the most common neurological disorders. In most instances ET is inherited as an autosomal dominant trait with age-related penetrance (virtually complete in advanced age); however, ET genetics remains elusive. The current study aims to identify possibly pathogenic genetic variants in a group of well-characterized ET families. Methods: 34 individuals from 14 families with dominant ET were clinically evaluated and studied by whole exome sequencing studies (after excluding trinucleotide expansion disorders). Results: Most patients had pure ET. In 4 families, exome studies could identify a genetic variant potentially able to significantly alter the protein structure (CADD >20, REVEL score > 0.25), shared by all the affected individuals (in CAMTA1 , FUS , MYH14, SGCE genes). In another family there were two variants in dominant genes ( PCDH9 and SQSTM1 ). Moreover, an interrupted "intermediate" trinucleotide expansion in ATXN1 ("SCA1") was identified in a further family with pure ET. Conclusion: Combining our observations together with earlier reports, we can conclude that ET genes confirmed in at least two families to date include CAMTA1 and FUS (reported here), as well as CACNA1G , NOTCH2NLC and TENM4. Most cases of familial ET, inherited with an autosomal dominant inheritance, may result from "mild" variants of many different genes that, when affected by more harmful genetic variants, lead to more severe neurological syndromes (still autosomal dominant). Thus, ET phenotype may be the "mild", incomplete manifestation of many other dominant neurogenetic diseases. These findings further support evidence of genetic heterogeneity for such disease(s).

The proven superior ductility of nanoglasses (NGs) makes them a promising second phase for metallic glass (MG) matrix composites. Here we evaluate the mechanical properties of MG-NG nanolaminate composites by performing molecular dynamics simulations of tensile loading. We focus on the effects of NG layer thickness and separation as well as the loading direction on the predicted strength and inelastic deformation profile. Our results reveal that nanolaminates with NG layers separated by more than 50 nm fail by shear banding. Meanwhile, the predicted nanolaminate strength versus MG volume fraction follows an inverse Hall-Petch relationship rather than the linear rule-of-mixtures. In contrast, by closely packing NG layers to 4.8 or 6.5 nm, the nanolaminates exhibit enhanced tensile ductility for tensile loading perpendicular or parallel to the MG-NG interfaces, respectively. Our results further reveal that the change in the loading direction causes the differences not only in the location of SB initiation but also the critical distance between NG layers for failure mode transition. Finally, the MG-NG nanolaminate structure with NG layers closely packed and interfaces oriented parallel to the loading direction is identified as the most effective heterostructure, which preserves superplasticity while producing a maximum strength of 2.35 GPa, a value 15% greater than that of monolithic NG with a grain size of 5 nm. Our work demonstrates that a nanolaminate combining MG and NG layers of suitable thicknesses is able to withstand large plastic deformations while maintaining the structural stability, and we expect that these results will inspire the development of novel strong and superplastic MG matrix composites that will broaden the possible applications of MGs.

Paroxysmal dyskinesias (PxDs) are involuntary, episodic moveents including any combination of dystonia, ballism, chorea, r athetosis [1]. The events may be precipitated by sudden volntary movements (paroxysmal kinesigenic dyskinesias) or may ccur spontaneously at rest (paroxysmal non-kinesigenic dyskineias precipitated by caffeine, alcohol, fatigue and emotional stress). n uncommon type of PxD is precipitated by exertion and is called aroxysmal exertion-induced dyskinesia (PED) [1]. Although most ases of PxD are primary, specific cause could be recognized such as ultiple sclerosis, vascular lesions, trauma, or acquired metabolic bnormalities [1].