32 research outputs found

    The problem of individualization of legal entities in terms of innovative development of the Russian Federation and the European Union economy

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    This article is a comprehensive analytical study of the problem of individualization of legal entities in terms of innovative development of the Russian Federation and the European Union. Using the latest methodology of scientific research, the authors provide a justification of the legal institution of individualization, as well as offer a wide range of means of individualization of innovation actors and participants, including in the virtual space of the Internet.peer-reviewe

    Varied Responses to a High m.3243A>G Mutation Load and Respiratory Chain Dysfunction in Patient-Derived Cardiomyocytes

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    The m.3243A>G mutation in mitochondrial tRNA-Leu(UUR) is one of the most common pathogenic mitochondrial DNA mutations in humans. The clinical manifestations are highly heterogenous and the causes for the drastic clinical variability are unknown. Approximately one third of patients suffer from cardiac disease, which often increases mortality. Why only some patients develop cardiomyopathy is unknown. Here, we studied the molecular effects of a high m.3243A>G mutation load on cardiomyocyte functionality, using cells derived from induced pluripotent stem cells (iPSC-CM) of two different m.3243A>G patients, only one of them suffering from severe cardiomyopathy. While high mutation load impaired mitochondrial respiration in both patients’ iPSC-CMs, the downstream consequences varied. mtDNA mutant cells from a patient with no clinical heart disease showed increased glucose metabolism and retained cellular ATP levels, whereas cells from the cardiac disease patient showed reduced ATP levels. In this patient, the mutations also affected intracellular calcium signaling, while this was not true in the other patient’s cells. Our results reflect the clinical variability in mitochondrial disease patients and show that iPSC-CMs retain tissue specific features seen in patients

    Varied Responses to a High m.3243A>G Mutation Load and Respiratory Chain Dysfunction in Patient-Derived Cardiomyocytes

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    The m.3243A>G mutation in mitochondrial tRNA-Leu(UUR) is one of the most common pathogenic mitochondrial DNA mutations in humans. The clinical manifestations are highly heterogenous and the causes for the drastic clinical variability are unknown. Approximately one third of patients suffer from cardiac disease, which often increases mortality. Why only some patients develop cardiomyopathy is unknown. Here, we studied the molecular effects of a high m.3243A>G mutation load on cardiomyocyte functionality, using cells derived from induced pluripotent stem cells (iPSC-CM) of two different m.3243A>G patients, only one of them suffering from severe cardiomyopathy. While high mutation load impaired mitochondrial respiration in both patients’ iPSC-CMs, the downstream consequences varied. mtDNA mutant cells from a patient with no clinical heart disease showed increased glucose metabolism and retained cellular ATP levels, whereas cells from the cardiac disease patient showed reduced ATP levels. In this patient, the mutations also affected intracellular calcium signaling, while this was not true in the other patient’s cells. Our results reflect the clinical variability in mitochondrial disease patients and show that iPSC-CMs retain tissue specific features seen in patients

    Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart

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    Vascular endothelial growth factor B (VEGF-B) is a potentmediator of vascular, metabolic, growth, and stress responses in the heart, but the effects on cardiac muscle and cardiomyocyte function are not known. The purpose of this study was to assess the effects of VEGF-B on the energy metabolism, contractile, and electrophysiological properties of mouse cardiac muscle and cardiac muscle cells. In vivo and ex vivo analysis of cardiac-specific VEGF-B TG mice indicated that the contractile function of the TG hearts was normal. Neither the oxidative metabolism of isolated TG cardiomyocytes nor their energy substrate preference showed any difference to WT cardiomyocytes. Similarly, myocyte Ca2+ signaling showed only minor changes compared to WT myocytes. However, VEGF-B overexpression induced a distinct electrophysiological phenotype characterized by ECG changes such as an increase in QRSp time and decreases in S and R amplitudes. At the level of isolated TG cardiomyocytes, these changes were accompanied with decreased action potential upstroke velocity and increased duration (APD60-70). These changes were partly caused by downregulation of sodium current (INa) due to reduced expression of Nav1.5. Furthermore, TG myocytes had alterations in voltage-gated K + currents, namely decreased density of transient outward current (Ito) and total K + current (Ipeak). At the level of transcription, these were accompanied by downregulation of Kv channel-interacting protein 2 (Kcnip2), a knownmodulatory subunit for Kv4.2/3 channel. Cardiac VEGF-B overexpression induces a distinct electrophysiological phenotype including remodeling of cardiomyocyte ion currents, which in turn induce changes in action potential waveform and ECG.Peer reviewe

    Challenging Diagnostics of Biofilm Associated Periprosthetic Infection in Immunocompromised Patient: A Clinical Case

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    Abstract BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication of joint arthroplasty. The identification of microorganisms in biofilm-related PJI is challenging yet significant stage of the treatment process. Medical microbiology methods, such as pure culture isolation, remain the gold standard. However, the error rate of classical methods may vary from 10% to as high as 42% due to the inability to detect bacteria growing within biofilms. Other methods of detection are being explored to improve the management of PJI. AIM: Accurate identification of PJI contributing microorganisms in a patient with acute postoperative PJI after total hip joint arthroplasty and systemic lupus erythematosus in anamnesis. METHODS: We used microbial culture methods followed by scanning electron microscopy (SEM). RESULTS: Perioperative an intraoperative cultural analysis of 8 different culture samples of tissue and prosthetic origin was insufficient for bacterial or fungal detection. Scanning electron microscopy revealed detailed biofilm visualisation on the surface of the prosthetic component. The biofilm exterior was composed of microbial clusters made of 10 or more cells with either pear- or bottle-shaped morphology, 3-6 mcm in length and 1.5-3 mcm in diameter. Rod-shaped microorganisms of 0.7-1 mcm length and up to 0.5 mcm in diameter were found adjacent to these clusters. CONCLUSION: Additional methods for PJI agents’ detection are time-and cost-effective in the case of the challenging diagnostics of biofilm-related PJI, particularly in immunocompromised patients. Using combined diagnostic approaches increases the accuracy of detection, justifies treatment strategies and improves clinical outcomes

    Natural Selection Equally Supports the Human Tendencies in Subordination and Domination: A Genome-Wide Study With in silico Confirmation and in vivo Validation in Mice

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    We proposed the following heuristic decision-making rule: “IF {an excess of a protein relating to the nervous system is an experimentally known physiological marker of low pain sensitivity, fast postinjury recovery, or aggressive, risk/novelty-seeking, anesthetic-like, or similar agonistic-intolerant behavior} AND IF {a single nucleotide polymorphism (SNP) causes overexpression of the gene encoding this protein} THEN {this SNP can be a SNP marker of the tendency in dominance} WHILE {underexpression corresponds to subordination} AND vice versa.” Using this decision-making rule, we analyzed 231 human genes of neuropeptidergic, non-neuropeptidergic, and neurotrophinergic systems that encode neurotrophic and growth factors, interleukins, neurotransmitters, receptors, transporters, and enzymes. These proteins are known as key factors of human social behavior. We analyzed all the 5,052 SNPs within the 70 bp promoter region upstream of the position where the protein-coding transcript starts, which were retrieved from databases Ensembl and dbSNP using our previously created public Web service SNP_TATA_Comparator (http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan/start.pl). This definition of the promoter region includes all TATA-binding protein (TBP)-binding sites. A total of 556 and 552 candidate SNP markers contributing to the dominance and the subordination, respectively, were uncovered. On this basis, we determined that 231 human genes under study are subject to natural selection against underexpression (significance p < 0.0005), which equally supports the human tendencies in domination and subordination such as the norm of a reaction (plasticity) of the human social hierarchy. These findings explain vertical transmission of domination and subordination traits previously observed in rodent models. Thus, the results of this study equally support both sides of the century-old unsettled scientific debate on whether both aggressiveness and the social hierarchy among humans are inherited (as suggested by Freud and Lorenz) or are due to non-genetic social education, when the children are influenced by older individuals across generations (as proposed by Berkowitz and Fromm)

    A squatting based framework to enhance network virtualization allocation in optical networks

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    This paper introduces a framework to enhance network virtualization allocation in optical networks. A new control plane approach for the new generation of electrical and optical networks technologies is presented. To increase resources utilization efficiency, a new layer above virtualized elements is introduced in order to take into account the demands in order to control the resources and infrastructures below. For that layer, a strategy based on a resource squatting model is presented.Peer Reviewe

    Design and analysis of a framework to enhance optical network utilization resources by means of virtualization

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    The time for an all-optical network is already here. The huge capacity of the optical resources, in backbones, distribution and access networks cannot be completely used by current services. The remainders can be used under the deployment of new models for service provisio ning. Network virtualizati on is considered as a serious candidate to enable the flexibl e provision of services in the future Internet. This paper introduces a framework to enhance network virtualization allocati on in optical networks. To increase resources utilization efficiency, a new layer above virtualized elements is introduced to map the demands over the resour ces and infrastructures. For that layer, a strategy based on a resource squa tting model is presented, modeled and analyzed.Peer ReviewedPostprint (published version

    Dynamic mechanical properties of polymer composites

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    Available from British Library Document Supply Centre-DSC:DX217728 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

    Design and analysis of a framework to enhance optical network utilization resources by means of virtualization

    No full text
    The time for an all-optical network is already here. The huge capacity of the optical resources, in backbones, distribution and access networks cannot be completely used by current services. The remainders can be used under the deployment of new models for service provisio ning. Network virtualizati on is considered as a serious candidate to enable the flexibl e provision of services in the future Internet. This paper introduces a framework to enhance network virtualization allocati on in optical networks. To increase resources utilization efficiency, a new layer above virtualized elements is introduced to map the demands over the resour ces and infrastructures. For that layer, a strategy based on a resource squa tting model is presented, modeled and analyzed.Peer Reviewe
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