5,578 research outputs found

    High ferritin levels have major effects on the morphology of erythrocytes in Alzheimer's disease

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    Introduction: Unliganded iron both contributes to the pathology of Alzheimer's disease (AD) and also changes the morphology of erythrocytes (RBCs). We tested the hypothesis that these two facts might be linked, i.e., that the RBCs of AD individuals have a variant morphology, that might have diagnostic or prognostic value. Methods: We included a literature survey of AD and its relationships to the vascular system, followed by a laboratory study. Four different microscopy techniques were used and results statistically compared to analyze trends between high and normal serum ferritin (SF) AD individuals. Results: Light and scanning electron microscopies showed little difference between the morphologies of RBCs taken from healthy individuals and from normal SF AD individuals. By contrast, there were substantial changes in the morphology of RBCs taken from high SF AD individuals. These differences were also observed using confocal microscopy and as a significantly greater membrane stiffness (measured using force-distance curves). Conclusion: We argue that high ferritin levels may contribute to an accelerated pathology in AD. Our findings reinforce the importance of (unliganded) iron in AD, and suggest the possibility both of an early diagnosis and some means of treating or slowing down the progress of this disease

    FSHD myoblasts fail to downregulate intermediate filament protein vimentin during myogenic differentiation.

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    Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant hereditary neuromuscular disorder. The clinical features of FSHD include weakness of the facial and shoulder girdle muscles followed by wasting of skeletal muscles of the pelvic girdle and lower extremities. Although FSHD myoblasts grown in vitro can be induced to differentiate into myotubes by serum starvation, the resulting FSHD myotubes have been shown previously to be morphologically abnormal. Aim. In order to find the cause of morphological anomalies of FSHD myotubes we compared in vitro myogenic differentiation of normal and FSHD myoblasts at the protein level. Methods. We induced myogenic differentiation of normal and FSHD myoblasts by serum starvation. We then compared protein extracts from proliferating myoblasts and differentiated myotubes using SDS-PAGE followed by mass spectrometry identification of differentially expressed proteins. Results. We demonstrated that the expression of vimentin was elevated at the protein and mRNA levels in FSHD myotubes as compared to normal myotubes. Conclusions. We demonstrate for the first time that in contrast to normal myoblasts, FSHD myoblasts fail to downregulate vimentin after induction of in vitro myogenic differentiation. We suggest that vimentin could be an easily detectable marker of FSHD myotube

    Rab6 and Rab11 Regulate Chlamydia trachomatis Development and Golgin-84-Dependent Golgi Fragmentation

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    Many intracellular pathogens that replicate in special membrane bound compartments exploit cellular trafficking pathways by targeting small GTPases, including Rab proteins. Members of the Chlamydiaceae recruit a subset of Rab proteins to their inclusions, but the significance of these interactions is uncertain. Using RNA interference, we identified Rab6 and Rab11 as important regulators of Chlamydia infections. Depletion of either Rab6 or Rab11, but not the other Rab proteins tested, decreased the formation of infectious particles. We further examined the interplay between these Rab proteins and the Golgi matrix components golgin-84 and p115 with regard to Chlamydia-induced Golgi fragmentation. Silencing of the Rab proteins blocked Chlamydia-induced and golgin-84 knockdown-stimulated Golgi disruption, whereas Golgi fragmentation was unaffected in p115 depleted cells. Interestingly, p115-induced Golgi fragmentation could rescue Chlamydia propagation in Rab6 and Rab11 knockdown cells. Furthermore, transport of nutrients to Chlamydia, as monitored by BODIPY-Ceramide, was inhibited by Rab6 and Rab11 knockdown. Taken together, our results demonstrate that Rab6 and Rab11 are key regulators of Golgi stability and further support the notion that Chlamydia subverts Golgi structure to enhance its intracellular development

    Simultaneous miRNA and mRNA transcriptome profiling of human myoblasts reveals a novel set of myogenic differentiation-associated miRNAs and their target genes

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    Background: miRNA profiling performed in myogenic cells and biopsies from skeletal muscles has previously identified miRNAs involved in myogenesis. Results: Here, we have performed miRNA transcriptome profiling in human affinity-purified CD56+ myoblasts induced to differentiate in vitro. In total, we have identified 60 miRNAs differentially expressed during myogenic differentiation. Many were not known for being differentially expressed during myogenic differentiation. Of these, 14 (miR-23b, miR-28, miR-98, miR-103, miR-107, miR-193a, miR-210, miR-324-5p, miR-324-3p, miR-331, miR-374, miR-432, miR-502, and miR-660) were upregulated and 6 (miR-31, miR-451, miR-452, miR-565, miR-594 and miR-659) were downregulated. mRNA transcriptome profiling performed in parallel resulted in identification of 6,616 genes differentially expressed during myogenic differentiation. Conclusions: This simultaneous miRNA/mRNA transcriptome profiling allowed us to predict with high accuracy target genes of myogenesis-related microRNAs and to deduce their functions

    Свойства и параметры обобщенных кодов Боуза – Чоудхури – Хоквингема

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    The Bose – Chaudhuri – Hocquenghem type of linear cyclic codes (BCH codes) is one of the most popular and widespread error-correcting codes. Their close connection with the theory of Galois fields gave an opportunity to create a theory of the norms of syndromes for BCH codes, namely, syndrome invariants of the G-orbits of errors, and to develop a theory of polynomial invariants of the G-orbits of errors. This theory as a whole served as the basis for the development of effective permutation polynomial-norm methods and error correction algorithms that significantly reduce the influence of the selector problem. To date, these methods represent the only approach to error correction with non-primitive BCH codes, the multiplicity of which goes beyond design boundaries. This work is dedicated to a special error-correcting code class – generic Bose – Chaudhuri – Hocquenghem codes or simply GBCH-codes. Sufficiently accurate evaluation of the quantity of such codes in each length was produced during our work. We have investigated some properties and connections between different GBCH-codes. Special attention was devoted to codes with constructive distances of 3 and 5, as those codes are usual for practical use. Their almost complete description is given in the range of lengths from 7 to 107. The paper contains a fairly clear theoretical classification of GBCH-codes. Special attention is paid to the corrective capabilities of the codes of this class, namely, to the calculation of the minimal distances of these codes with various parameters. The codes are found whose corrective capabilities significantly exceed those of the well-known GBCH-codes with the same design parameters.Семейство линейных циклических кодов Боуза – Чоудхури – Хоквингема (БЧХ-кодов) относится к классу наиболее популярных в теории и наиболее массовых в практическом применении помехоустойчивых кодов. Их тесная связь с теорией полей Галуа позволила создать для БЧХ-кодов теорию норм синдромов – синдромных инвариантов Г-орбит ошибок, развить теорию полиномиальных инвариантов G-орбит ошибок. Данная теория в целом послужила основой разработки эффективных перестановочных полиномиально-норменных методов и алгоритмов коррекции ошибок, на порядок снижающих влияние проблемы селектора. На сегодняшний день эти методы представляют единственный подход к коррекции ошибок непримитивными БЧХ-кодами, кратность которых выходит за пределы конструктивных границ. Настоящая работа посвящена определению и исследованию помехоустойчивых обобщенных двоичных кодов Боуза – Чоудхури – Хоквингема (ОБЧХ-кодов). Произведена достаточно точная оценка количества этих кодов каждой конкретной длины. Установлен ряд свойств и взаимосвязей ОБЧХ-кодов. Наиболее подробно рассмотрены ОБЧХкоды с конструктивным расстоянием три и пять, так как подобные коды чаще всего и используются на практике. Дано их практически полное описание в диапазоне длин от 7 до 107. Работа содержит достаточно четкую теоретическую классификацию ОБЧХ-кодов. Особое внимание уделено корректирующим возможностям кодов данного класса – расчету минимальных расстояний этих кодов с различными параметрами. Найдены коды, корректирующие возможности которых существенно превосходят таковые у известных БЧХ-кодов с теми же конструктивными параметрами

    New record of Abralia (Heterabralia) siedleckyi Lipinski, 1983 (Cephalopoda: Enoploteuthidae) from south-eastern Arabian Sea with some remarks about its biology

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    Specimens of oceanic squid, Abralia (Heterabralia) siedleckyi Lipinski, 1983 were collected from the south-eastern Arabian Sea using midwater trawl (horizontally at 200 m depth) during night operations in two cruises on 18 April 2015 and 26 February 2017. Description and morphological measurements of the specimens are provided. The record of this mesopelagic squid from the Arabian Sea is an addition to the cephalopod fauna of the Indian Ocean and India. The statolith based age analysis indicates that a 29.1 mm dorsal mantle length specimen had 93 day’s age with a growth rate of 0.31 mm DML/day

    Loss of neuronal 3d chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction

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    The interior of the neuronal cell nucleus is a highly organized three-dimensional (3D) structure where regions of the genome that are linearly millions of bases apart establish sub-structures with specialized functions. To investigate neuronal chromatin organization and dynamics in vivo, we generated bitransgenic mice expressing GFP-tagged histone H2B in principal neurons of the forebrain. Surprisingly, the expression of this chimeric histone in mature neurons caused chromocenter declustering and disrupted the association of heterochromatin with the nuclear lamina. The loss of these structures did not affect neuronal viability but was associated with specific transcriptional and behavioural deficits related to serotonergic dysfunction. Overall, our results demonstrate that the 3D organization of chromatin within neuronal cells provides an additional level of epigenetic regulation of gene expression that critically impacts neuronal function. This in turn suggests that some loci associated with neuropsychiatric disorders may be particularly sensitive to changes in chromatin architecture
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