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Author(s): Gatto, Emilia M; Walker, Ruth H; Gonzalez, Claudio; Cesarini, Martin; Cossu, Giovanni; Stephen, Christopher D; Balint, Bettina; Rodriguez-Violante, Mayela; Jankovic, Joseph; Morgante, Francesca; Jinnah, Hyder A; Rare Movement Disorders Study Group of the International Parkinson Disease, Movement Disorders Society | Abstract: Background and purposeDespite enormous advances in identifying genetic variants responsible for many neurological diseases, access to genetic testing may be limited in clinical practice. The objective of this study was to assess worldwide access to genetic tests for movement disorders and factors impacting their utilization.MethodsThe Rare Movement Disorders Study Group of the International Parkinson and Movement Disorder Society designed an online survey electronically mailed to all 7815 members.ResultsSurvey data completed by 1269 participants from 109 countries were analysed. Limited access to geneticists and genetic counsellors was reported in many world regions compared to Europe and North America. Availability of genetic testing was limited, with rates of access lower than 50%. Genetic testing for chorea was the most commonly available. For parkinsonism, dystonia, ataxia, hereditary spastic paraplegias and metabolic disorders, there was limited access to genetic testing in all countries compared to Europe and North America, with significant differences found for Africa, Central/South America, Asia. In many regions, genetic testing was supported by either private or public funding. Genetic testing was free of charge in Europe according to 63.5% of respondents. In North America, Africa, Central/South America, Asia and the Middle East access to free of charge genetic testing was by far significantly lower compared to Europe.ConclusionsThis survey highlights difficulties in accessing genetic testing and individuals with expertise in genetics at the worldwide level. In addition, major disparities in genetic testing amongst world regions are highlighted, probably due to a variety of factors including financial barriers.

Most research in comparative cognition focuses on measuring if animals manage certain tasks; fewer studies explore how animals might solve them. We investigated bumblebees’ scanning strategies in a numerosity task, distinguishing patterns with two items from four and one from three, and subsequently transferring numerical information to novel numbers, shapes, and colors. Video analyses of flight paths indicate that bees do not determine the number of items by using a rapid assessment of number (as mammals do in “subitizing”); instead, they rely on sequential enumeration even when items are presented simultaneously and in small quantities. This process, equivalent to the motor tagging (“pointing”) found for large number tasks in some primates, results in longer scanning times for patterns containing larger numbers of items. Bees used a highly accurate working memory, remembering which items have already been scanned, resulting in fewer than 1% of re-inspections of items before making a decision. Our results indicate that the small brain of bees, with less parallel processing capacity than mammals, might constrain them to use sequential pattern evaluation even for low quantities.

Background Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. Methods We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. Results Genome-wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69-10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10-7 ). Conclusions We found that although overall genome-wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early-onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome-wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population. © 2020 International Parkinson and Movement Disorder Society.

The role of the conformationally constrained α-aminoisobutyric acid (Aib) residue in the aggregation and self-assembly properties of oligopeptides is discussed, critically reviewing our recent work in the field. In this connection, three significant case studies are presented: (i) aggregation propensity of Aib homo-oligopeptides of different length; (ii) perturbation of the conformational and aggregation properties of Ala-based pentapeptides by a single Aib versus Ala substitution; and (iii) build up of self-assembled monolayers formed by Aib homo-hexapeptide building blocks. The peptides investigated were all functionalized by a fluorescent probe, that is, a naphthyl group in the first case-study and a pyrenyl group in the other two, with the aim at applying optical spectroscopy techniques and evaluating the relevance of aromatic interactions in the aggregation process. Microscopy techniques at nanometric resolution and results of molecular dynamics simulations are also presented to analyze how the conformational properties of the peptide building blocks would affect the morphology of the peptide aggregates from the nanoscale to the mesoscale. Copyright © 2017 European Peptide Society and John WileySons, Ltd.

Objective: To evaluate how different bracket-slot design characteristics affect the forces released by superelastic nickel-titanium (NiTi) alignment wires at different amounts of wire deflection. Materials and Methods: A three-bracket bending and a classic-three point bending testing apparatus were used to investigate the load-deflection properties of one superelastic 0.014-inch NiTi alignment wire in different experimental conditions. The selected NiTi archwire was tested in association with three bracket systems: (1) conventional twin brackets with a 0.018-inch slot, (2) a self-ligating bracket with a 0.018-inch slot, and (3) a self-ligating bracket with a 0.022-inch slot. Wire specimens were deflected at 2 mm and 4 mm. Results: Use of a 0.018-inch slot bracket system, in comparison with use of a 0.022-inch system, increases the force exerted by the superelastic NiTi wires at a 2-mm deflection. Use of a self-ligating bracket system increases the force released by NiTi wires in comparison with the conventional ligated bracket system. NiTi wires deflected to a different maximum deflection (2 mm and 4 mm) release different forces at the same unloading data point (1.5 mm). Conclusion: Bracket design, type of experimental test, and amount of wire deflection significantly affected the amount of forces released by superelastic NiTi wires (P < .05). This phenomenon offers clinicians the possibility to manipulate the wire's load during alignment.

Interactions between peptides are relevant from a biomedical point of view, in particular for the role played by their aggregates in different important pathologies, and also because peptide aggregates represent promising scaffolds for innovative materials. In the present article, the aggregation properties of the homo-peptides formed by α-aminoisobutyric acid (U) residues are discussed. The peptides investigated have chain lengths between six and 15 residues and comprise benzyl and naphthyl groups at the N- and C-termini, respectively. Spectroscopic experiments and molecular dynamics simulations show that the shortest homo-peptide, constituted by six U, does not exhibit any tendency to aggregate under the conditions examined. On the other hand, the homologous peptide with 15 U forms very stable and compact aggregates in 70/30(v/v) methanol/water solution. Atomic force microscopy images indicate that these aggregates promote formation of long fibrils once they are deposited on a mica surface. The aggregation phenomenon is mainly due to hydrophobic interactions occurring between very stable helical structures, and the aromatic groups in the peptides seem to play a minor role.

The photocurrent generation properties of mono- and bi-component peptide-based self-assembled monolayers (SAMs) immobilized on a gold surface were studied by electrochemical and spectroscopic techniques. The peptides investigated comprised almost exclusively C(alpha)-tetrasubstituted alpha-amino acids. These non-coded residues, because of their unique conformational properties, forced the peptide backbone to attain a helical conformation, as confirmed by X-ray crystal structure and CD determinations in solution. The peptide helical structure promoted the formation of a stable SAM on the gold surface, characterized by an electric macrodipole directed from the C(delta(-)) to the N(delta(+)) terminus, that remarkably affected the electron transfer (ET) process through the peptide chain. The peptides investigated were derivatized with chromophores strongly absorbing in the UV region to enhance the efficiency of the photocurrent generation (antenna effect). The influence of the nature of the peptide-gold interface on the ET process (junction effect) was analyzed by comparing the photocurrent generation process in peptide SAMs immobilized on a gold surface through Au-S linkages with that in a bi-component SAM embedding a photoactive peptide into the linked palisade formed by disulfide-functionalized peptides.