Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities.

OBJECTIVES: The majority of people with suspected genetic dystonia remain undiagnosed after maximal investigation, implying that a number of causative genes have not yet been recognized. We aimed to investigate this paucity of diagnoses. METHODS: We undertook weighted burden analysis of whole-exome sequencing (WES) data from 138 individuals with unresolved generalized dystonia of suspected genetic etiology, followed by additional case-finding from international databases, first for the gene implicated by the burden analysis (VPS16), and then for other functionally related genes. Electron microscopy was performed on patient-derived cells. RESULTS: Analysis revealed a significant burden for VPS16 (Fisher's exact test p value, 6.9 × 109 ). VPS16 encodes a subunit of the homotypic fusion and vacuole protein sorting (HOPS) complex, which plays a key role in autophagosome-lysosome fusion. A total of 18 individuals harboring heterozygous loss-of-function VPS16 variants, and one with a microdeletion, were identified. These individuals experienced early onset progressive dystonia with predominant cervical, bulbar, orofacial, and upper limb involvement. Some patients had a more complex phenotype with additional neuropsychiatric and/or developmental comorbidities. We also identified biallelic loss-of-function variants in VPS41, another HOPS-complex encoding gene, in an individual with infantile-onset generalized dystonia. Electron microscopy of patient-derived lymphocytes and fibroblasts from both patients with VPS16 and VPS41 showed vacuolar abnormalities suggestive of impaired lysosomal function. INTERPRETATION: Our study strongly supports a role for HOPS complex dysfunction in the pathogenesis of dystonia, although variants in different subunits display different phenotypic and inheritance characteristics. ANN NEUROL 2020;88:867-877

The voice control of mechatronic devices the concept of didactic station

W artykule zaprezentowano algorytmy zamiany głosu ludzkiego na postać cyfrową i na tej podstawie rozpoznawanie wydawanych komend. Przedstawiono opis algorytmu MFCC oraz jego aplikację działającą na platformie Raspberry Pi. Opisano spotykane open-source’owe programy umożliwiające rozpozanawanie mowy, działające w środowisku LINUX. Zaprezentowano koncepcję stanowiska dydaktycznego realizującego proste komendy głosowe. Przedstawiono rezultaty testów sprawdzających.The article features basic algorithms which are responsible for converting human voice into digital form. It also describes MFCC algorithm and the steps required to put it into practice. It includes presentation of the primary open-source software programs, that allow speech recognition in Linux environment, on the platform Raspberry Pi. At the end, the article presents a concept of didactic station, performing simple voice commands using Jasper program and its possibility to use in future

Analysis of the permanent magnets magnetization on the transients of the electrical and mechanical quantities of a brushless dc motor

Circuit-field models of the brushless DC motor with parallel and radial magnets magnetization were developed. Transients of the electrical and mechanical quantities of the motor were determined at parallel and radial magnets magnetization. Experimental verification was carried out. The computed and the measured transients were compared

Population size and distribution of the capercaillie in Poland in the 21st century

The data on the distribution and number of the capercaillie Tetrao urogallus in Poland for the period from the end of the 20th century up to 2017−2018 is presented. The capercaillie is a sedentary forest grouse living in old mountain forests and within the boreal zone. Since more than a century, the decrease in the numbers of the species has been observed, interlinked with the extinction of isolated populations. Within the present borders of Poland, a 1925 questionnaire study noted 2200−2700 individuals. In the 1960s, the national population was estimated at 1700−2000 birds, living in five isolated populations. In 1985−1995, the population numbers of the capercaillie dropped to approx. 466−700 individuals in four regions, and in 2000 it was estimated at 470−570 birds. According to the results of the censuses performed in 2017−2018, the size of the capercaillie population risen to 523−631 individuals and 59−69 lekking grounds. Currently the capercaillie occurs in four isolated regions. These are the Western Carpathians (the Beskid Sądecki, Tatry, Gorce, Babia Góra, Beskid Żywiecki, and the Beskid Śląski ranges) where 284−326 individuals live and 35−41 leks are active. In the Solska and the Lasy Janowskie Forests (Lublin region), the population was estimated at 132−184 individuals and 12−13 lekking grounds. In the Augu− stów Forest (Podlasie region) 36−46 individuals and 5−7 leks were found. In the Bory Dolnośląskie Forest, where native capercaillies got extinct during the last decade, the reintroduction program resulted in the rebuilding of their 65−75 population (with 6−7 leks). The restitution of the species in the Piska Forest has begun. During the last 20 years, populations in the Carpathian national parks have been stable, although fluctuating in numbers. The increase in the number of individuals in the Augustów Forest as well as in the Sądecki and Beskid Śląski Mountains is an after−effect of the release of birds from breeding centers or translocations. In other strongholds, fluctuations or decreases have been recorded, including wisible in the Beskid Żywiecki Mountains