Self-study guide to developing English linguistic competences for students of Computer Sciences

Методичні вказівки призначені для самостійної роботи студентів ІТ спеціальностей над опануванням фахової термінології та мають на меті допомогти студентам І та ІІ курсів самостійно працювати над розширенням словникового запасу, розвитком вмінь здобування інформації з англомовних текстових джерел

ВНЕСОК КРАЄЗНАВЦЯ В.В. БІНКЕВИЧА У ДОСЛІДЖЕННЯ АРХЕОЛОГІЧНИХ ПАМ’ЯТОК НАДПОРІЖЖЯ

Розглянуто творчий шлях визначного дніпропетровського краєзнавця Володимира Васильовича Бінкевича.The author considers creative way of the famous dnipropetrovsk student of local lore Volodimir Vasil’ovich Binkevich

Colloids in light fields: particle dynamics in random and periodic energy landscapes

The dynamics of colloidal particles in potential energy landscapes have mainly been investigated theoretically. In contrast, here we discuss the experimental realization of potential energy landscapes with the help of light fields and the observation of the particle dynamics by video microscopy. The experimentally observed dynamics in periodic and random potentials are compared to simulation and theoretical results in terms of, e.g. the mean-squared displacement, the time-dependent diffusion coefficient or the non-Gaussian parameter. The dynamics are initially diffusive followed by intermediate subdiffusive behaviour which again becomes diffusive at long times. How pronounced and extended the different regimes are, depends on the specific conditions, in particular the shape of the potential as well as its roughness or amplitude but also the particle concentration. Here we focus on dilute systems, but the dynamics of interacting systems in external potentials, and thus the interplay between particle-particle and particle-potential interactions, is also mentioned briefly. Furthermore, the observed dynamics of dilute systems resemble the dynamics of concentrated systems close to their glass transition, with which it is compared. The effect of certain potential energy landscapes on the dynamics of individual particles appears similar to the effect of interparticle interactions in the absence of an external potential

Structural and functional analyses of the shedding protease ADAM17 in HoxB8-Immortalized macrophages and dendritic-like cells

A disintegrin and metalloproteinase (ADAM) 17 has been implicated in many shedding processes. Major substrates of ADAM17 are TNF-α, IL-6R, and ligands of the epidermal growth factor receptor. The essential role of the protease is emphasized by the fact that ADAM17 deficiency is lethal in mice. To study ADAM17 function in vivo, we generated viable hypomorphic ADAM17 mice called ADAM17ex/ex mice. Recent studies indicated regulation of proteolytic ADAM17 activity by cellular processes such as cytoplasmic phosphorylation and removal of the prodomain by furin cleavage. Maturation and thus activation of ADAM17 is not fully understood. So far, studies of ADAM17 maturation have been mainly limited to mouse embryonic fibroblasts or transfected cell lines relying on nonphysiologic stimuli such as phorbol esters, thus making interpretation of the results difficult in a physiologic context. In this article, we present a robust cell system to study ADAM17 maturation and function in primary cells of the immune system. To this end, HoxB8 conditionally immortalized macrophage precursor cell lines were derived from bone marrow of wild-type and hypomorphic ADAM17ex/ex mice, which are devoid of measurable ADAM17 activity. ADAM17 mutants were stably expressed in macrophage precursor cells, differentiated to macrophages under different growth factor conditions (M-CSF versus GM-CSF), and analyzed for cellular localization, proteolytic activity, and podosome disassembly. Our study reveals maturation and activity of ADAM17 in a more physiological-immune cell system. We show that this cell system can be further exploited for genetic modifications of ADAM17 and for studying its function in immune cells

Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models

Parkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While the exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggests the involvement of autophagic as well as lysosomal deficiencies. Because CTSD (cathepsin D) has been proposed to be the major lysosomal protease involved in SNCA degradation, its deficiency has been linked to the presence of insoluble SNCA conformers in the brain of mice and humans as well as to the transcellular transmission of SNCA aggregates. We here postulate that SNCA degradation can be enhanced by the application of the recombinant human proform of CTSD (rHsCTSD). Our results reveal that rHsCTSD is efficiently endocytosed by neuronal cells, correctly targeted to lysosomes and matured to an enzymatically active protease. In dopaminergic neurons derived from induced pluripotent stem cells (iPSC) of PD patients harboring the A53T mutation within the SNCA gene, we confirm the reduction of insoluble SNCA after treatment with rHsCTSD. Moreover, we demonstrate a decrease of pathological SNCA conformers in the brain and within primary neurons of a CTSD-deficient mouse model after dosing with rHsCTSD. Boosting lysosomal CTSD activity not only enhanced SNCA clearance, but also restored endo-lysosome and autophagy function in human and murine neurons as well as tissue. Our findings indicate that CTSD is critical for SNCA clearance and function. Thus, enzyme replacement strategies utilizing CTSD may also be of therapeutic interest for the treatment of PD and other synucleinopathies aiming to decrease the SNCA burden.authorsversionepub_ahead_of_prin

Структура вірусних діарей у дітей на Сумщині

Гострі кишкові інфекції (ГКІ) стійко посідають одне з провідних місць серед усіх інфекційних захворювань, характеризуються широкою поширеністю, високою частотою розвитку тяжких форм і ускладнень. Прогрес у галузі лабораторних методів діагностики дозволив істотно розширити уявлення про етіологічні чинники хвороби: у країнах, що розвиваються, домінують діарейні інфекції бактерійної етіології, а в економічно розвинених країнах - вірусної. При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/3228

Efficient RT-QuIC seeding activity for \u3b1-synuclein in olfactory mucosa samples of patients with Parkinson's disease and multiple system atrophy

Background: Parkinson's disease (PD) is a neurodegenerative disorder whose diagnosis is often challenging because symptoms may overlap with neurodegenerative parkinsonisms. PD is characterized by intraneuronal accumulation of abnormal \u3b1-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of either \u3b1-synuclein, as in the case of Multiple System Atrophy (MSA) or tau, as in the case of Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP), in other disease-specific brain regions. Definite diagnosis of all these diseases can be formulated only neuropathologically by detection and localization of \u3b1-synuclein or tau aggregates in the brain. Compelling evidence suggests that trace-amount of these proteins can appear in peripheral tissues, including receptor neurons of the olfactory mucosa (OM). Methods: We have set and standardized the experimental conditions to extend the ultrasensitive Real Time Quaking Induced Conversion (RT-QuIC) assay for OM analysis. In particular, by using human recombinant \u3b1-synuclein as substrate of reaction, we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induce \u3b1-synuclein aggregation, and compared their seeding ability to that of OM samples collected from patients with clinical diagnoses of CBD and PSP. Results: Our results showed that a significant percentage of MSA and PD samples induced \u3b1-synuclein aggregation with high efficiency, but also few samples of patients with the clinical diagnosis of CBD and PSP caused the same effect. Notably, the final RT-QuIC aggregates obtained from MSA and PD samples owned peculiar biochemical and morphological features potentially enabling their discrimination. Conclusions: Our study provide the proof-of-concept that olfactory mucosa samples collected from patients with PD and MSA possess important seeding activities for \u3b1-synuclein. Additional studies are required for (i) estimating sensitivity and specificity of the technique and for (ii) evaluating its application for the diagnosis of PD and neurodegenerative parkinsonisms. RT-QuIC analyses of OM and cerebrospinal fluid (CSF) can be combined with the aim of increasing the overall diagnostic accuracy of these diseases, especially in the early stages

Root‐lesion nematodes of potato: current status of diagnostics, pathogenicity and management

Root‐lesion nematodes of the genus Pratylenchus are migratory endoparasites with worldwide economic impact on several important crops including potato, where certain species like P. penetrans, P. neglectus and P. scribneri reduce the yield and quality of potato tubers. Morphological identification of Pratylenchus spp. is challenging, and recent advancements in molecular techniques provide robust and rapid diagnostics to differentiate species without need of specialist skills. However, the fact that molecular diagnostics are not available for all Pratylenchus species means that there are limitations in worldwide application. In general, root‐lesion nematodes are difficult to manage once introduced into agricultural land and damage can be related to pathogenicity and population densities. In addition, root‐lesion nematodes interact with fungi such as V. dahliae, resulting in disease complexes that enhance the damage inflicted on the potato crop. Management interventions are often focused on limiting nematode reproduction before planting crops and include the application of nematicides, and cultural practices such as crop rotation, cover crops, biofumigation, and biological control. Understanding the limitations of the available crop protection strategies is important and there are many gaps for further study. This review discusses the status of the diagnosis, distribution, pathogenicity and management of the main species of root‐lesion nematodes, reported to infect potatoes worldwide, and highlights areas for potential future research

A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease

Common variants of about 20 genes contributing to AD risk have so far been identified through genome-wide association studies (GWAS). However, there is still a large proportion of heritability that might be explained by rare but functionally important variants. One of the so far identified genes with rare AD causing variants is ADAM10. Using whole-genome sequencing we now identified a single rare nonsynonymous variant (SNV) rs142946965 [p.R215I] in ADAM17 co-segregating with an autosomal-dominant pattern of late-onset AD in one family. Subsequent genotyping and analysis of available whole-exome sequencing data of additional case/control samples from Germany, UK, and USA identified five variant carriers among AD patients only. The mutation inhibits pro-protein cleavage and the formation of the active enzyme, thus leading to loss-of-function of ADAM17 alpha-secretase. Further, we identified a strong negative correlation between ADAM17 and APP gene expression in human brain and present in vitro evidence that ADAM17 negatively controls the expression of APP. As a consequence, p.R215I mutation of ADAM17 leads to elevated Aß formation in vitro. Together our data supports a causative association of the identified ADAM17 variant in the pathogenesis of AD