Удосконалення моделей управління проектами створення систем управління інформаційною безпекою

Рудник, О. В. Удосконалення моделей управління проектами створення систем управління інформаційною безпекою = Improving project management models for creating information project management systems : магістерська робота ; спец. 122 “Комп’ютерні науки“ / О. В. Рудник ; наук. кер. В. Д. Гогунський. – Миколаїв : НУК, 2020. – 94 с.Рудник О. В. Удосконалення моделей управління проектами створення систем управління інформаційною безпекою. – На правах рукопису. Магістерська робота за спеціальністю 122 – Комп’ютерні науки, освітня програма – Управління проектами. Національний університет кораблебудування ім. адм. Макарова. Миколаїв, 2020. В данній магістерській роботі було проведено удосконалення моделей управління проектами створення систем управління інформаційною безпекою. В процесі виконання роботи був проведенний аналіз основних методів та функцій управління данним проектом, їх вплив та значення як для кожного окремого етапу проекту (ключового та другорядного), так і для всього проекту в цілому. В процесі аналізу на окремих єтапах виконання роботи були використані наступні методи та підходи: • Графоаналітичний метод дослідження потоків інформації. • Метод схем інформаційних зв’язків. • Метод аналізу ієрархій. • Метод аналізу дерева відмов. • Мотивація персоналу Данні підходи дозволили не лише виявити потенційні проблеми в управлінні проектом створення СУІБ, але й можливі шляхи та підходи стосовно їх усунення. Все це дозволило як підвищити єфективність управління процесів проекту, так і сприяло виявленню можливих шляхів зменшення витрат по проекту.Rudnik O. V. Improving project management models for creating information project management systems. – On the rights of the manuscript. Master's thesis in 122-Computer Science, educational program - Project Management. National University of Shipbuilding. adm. Makarova. Nikolaev, 2020. In this master's work was carried out improvements to create models of project management systems, information security management. In carrying out the work was carried out by analysis of the basic techniques and management functions in this project, their impact and value for each phase of the project (and a minor key), and for the whole project. During the analysis phase of individual performance were used the following methods and approaches: • Graphic-analytical method for studying the flow of information. • A description of the flow of information in the form of a graph. • The method of information communications circuits. • The method of analysis of hierarchies. • The method of fault tree analysis. • Motivation of staff These approaches have allowed not only to identify potential problems in project management to create an ISMS and possible ways and approaches to address them. All this is possible how to improve management processes efektivnist project and spiyalo identify possible ways to reduce project costs

Bi-allelic <em>ACBD6</em> variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne (YnMyr) chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), aged 1-50 years, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%) and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%) and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%) and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each) as well as hypertrophy of the clava (24%) were common neuroimaging findings. Acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localization and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-myristoylation was similarly affected in acbd6-deficient zebrafish and X. tropicalis models, including Fus, Marcks and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders

Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this recordData availability: The data that support the findings of this study are available from the corresponding author, upon reasonable request. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE24 partner repository with the dataset identifiers PXD024957 (YnMyr chemical proteomics in human cells), PXD043676 (YnMyr chemical proteomics in zebrafish), PXD043679 (zebrafish whole proteome), PXD043677 (YnMyr chemical proteomics in X. tropicalis) and PXD043680 (X. tropicalis whole proteome).The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Utilizing exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), with ages ranging from 1 to 50 years old, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%), and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%), and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava (24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism, and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localisation and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders