81 research outputs found

    The Russian press headlines denoting China

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    This article discusses the newspaper headlines of Russian mass newspapers ("Arguments and facts", "Komsomolskaya Pravda"). It is not a secret that the impact of printed information flows surpasses the influence of all other types of mass media: radio, television, Internet resources. The language of articles is an indicator of the processes taking place in different areas of the Russian language. Recently journalists have observed the strengthening of Russian-Chinese relations. As a result - the emergence of a large number of articles about the life of the neighboring country. The aim of the work is to study the headlines denoting Chin

    Conformational spread as a mechanism for cooperativity in the bacterial flagellar switch

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    The bacterial flagellar switch that controls the direction of flagellar rotation during chemotaxis has a highly cooperative response. This has previously been understood in terms of the classic two-state, concerted model of allosteric regulation. Here, we used high-resolution optical microscopy to observe switching of single motors and uncover the stochastic multistate nature of the switch. Our observations are in detailed quantitative agreement with a recent general model of allosteric cooperativity that exhibits conformational spread—the stochastic growth and shrinkage of domains of adjacent subunits sharing a particular conformational state. We expect that conformational spread will be important in explaining cooperativity in other large signaling complexes

    Six-month therapy of CGRP monoclonal antibodies in real-world clinical practice: an interim analysis of efficacy and safety data

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    Introduction. Migraine is one of the most common disabling neurological disorders. Recently developed monoclonal antibodies to calcitonin gene-related peptide (CGRP) or its receptor are the first targeted medication for preventive therapy of both episodic and chronic migraine. They have been thoroughly investigated in clinical trials; however, there is little data from real-world clinical practice available to date. The aim of this study is to assess the efficacy and safety of 6 months of treatment with erenumab in real-world clinical practice and investigate the effect of the drug on the patients’ sensitivity to medicines for migraine headaches relief and patient satisfaction after treatment.Materials and methods. Our observational cohort prospective study included patients in our Headache Clinic prescribed monoclonal antibodies blocking the  CGRP-receptor  – erenumab. During the  investigation, we evaluated the  previous preventive therapy and its efficacy, the number of days with migraine per month, adverse events occurring during the erenumab treatment, depression and anxiety (HADS), migraine disability (MIDAS), the presence of allodynia (ACS-12) and improved response to acute therapy after treatment. A total of 42 patients participated in the study: 6 men, 36 women, the average age was 43.9 ± 12.2. Of them, 38 patients (90%) had chronic migraine. Thirty-two patients (76%) had previously been prescribed preventive therapy, which proved ineffective, and 10 patients (24%) had not once received any type of migraine prevention.Results. Among our patients, we identified 11 patients with resistant migraine and one patient with refractory migraine. During the study, two patients dropped out due to adverse events (constipation). Thirty patients continued the administration of erenumab 70 mg for at least six months. The average number of migraine days per month before treatment was 22.8, and after six months of treatment, it dropped to 7.3. Twenty-nine patients (72.5%) also noted that the response to acute headache treatment improved after the therapy.Conclusion. The results of our study are consistent with the international experience of using erenumab and confirm its effectiveness for migraine preventive therapy, including difficult-to-treat migraine cases. However, further studies with more participants and evaluation of predictors of successful monoclonal antibody therapy are still needed

    Phenotypic Variation and Bistable Switching in Bacteria

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    Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

    Stochastic dynamics and mean field approach in a system of three interacting species

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    The spatio-temporal dynamics of three interacting species, two preys and one predator, in the presence of two different kinds of noise sources is studied. To describe the spatial distributions of the species we use a model based on Lotka-Volterra equations. A correlated dichotomous noise acts on \beta, the interaction parameter between the two preys, and a multiplicative white noise affects directly the dynamics of each one of the three species. We study the time behaviour of the three species in single site for different values of the multiplicative noise intensity, finding noise-induced oscillations of the three species densities with an anticorrelated behaviour of the two preys. Afterwards, by considering a spatially extended system formed by a two-dimensional lattice with N sites and applying a mean field approach, we get the corresponding moment equations in Gaussian approximation. Within this formalism we obtain the time behaviour of the first and second order moments for different values of multiplicative noise intensity, with \beta(t) subject to the same dichotomous noise source. Finally, we compare our results with those obtained by using a coupled map lattice model, consisting of a time discrete version of the Lotka-Volterra equations.Comment: 21 pages, 7 figures. Submitted to Centr. Eur. J. Phy

    On the Origin and Characteristics of Noise-Induced Lévy Walks of E. Coli

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    Lévy walks as a random search strategy have recently attracted a lot of attention, and have been described in many animal species. However, very little is known about one of the most important issues, namely how Lévy walks are generated by biological organisms. We study a model of the chemotaxis signaling pathway of E. coli, and demonstrate that stochastic fluctuations and the specific design of the signaling pathway in concert enable the generation of Lévy walks. We show that Lévy walks result from the superposition of an ensemble of exponential distributions, which occurs due to the shifts in the internal enzyme concentrations following the stochastic fluctuations. With our approach we derive the power-law analytically from a model of the chemotaxis signaling pathway, and obtain a power-law exponent , which coincides with experimental results. This work provides a means to confirm Lévy walks as natural phenomenon by providing understanding on the process through which they emerge. Furthermore, our results give novel insights into the design aspects of biological systems that are capable of translating additive noise on the microscopic scale into beneficial macroscopic behavior

    Noisy-threshold control of cell death

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    <p>Abstract</p> <p>Background</p> <p>Cellular responses to death-promoting stimuli typically proceed through a differentiated multistage process, involving a lag phase, extensive death, and potential adaptation. Deregulation of this chain of events is at the root of many diseases. Improper adaptation is particularly important because it allows cell sub-populations to survive even in the continuous presence of death conditions, which results, among others, in the eventual failure of many targeted anticancer therapies.</p> <p>Results</p> <p>Here, I show that these typical responses arise naturally from the interplay of intracellular variability with a threshold-based control mechanism that detects cellular changes in addition to just the cellular state itself. Implementation of this mechanism in a quantitative model for T-cell apoptosis, a prototypical example of programmed cell death, captures with exceptional accuracy experimental observations for different expression levels of the oncogene Bcl-x<sub>L </sub>and directly links adaptation with noise in an ATP threshold below which cells die.</p> <p>Conclusions</p> <p>These results indicate that oncogenes like Bcl-x<sub>L</sub>, besides regulating absolute death values, can have a novel role as active controllers of cell-cell variability and the extent of adaptation.</p

    Noise Filtering Strategies of Adaptive Signaling Networks: The Case of E. Coli Chemotaxis

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    Two distinct mechanisms for filtering noise in an input signal are identified in a class of adaptive sensory networks. We find that the high frequency noise is filtered by the output degradation process through time-averaging; while the low frequency noise is damped by adaptation through negative feedback. Both filtering processes themselves introduce intrinsic noises, which are found to be unfiltered and can thus amount to a significant internal noise floor even without signaling. These results are applied to E. coli chemotaxis. We show unambiguously that the molecular mechanism for the Berg-Purcell time-averaging scheme is the dephosphorylation of the response regulator CheY-P, not the receptor adaptation process as previously suggested. The high frequency noise due to the stochastic ligand binding-unbinding events and the random ligand molecule diffusion is averaged by the CheY-P dephosphorylation process to a negligible level in E.coli. We identify a previously unstudied noise source caused by the random motion of the cell in a ligand gradient. We show that this random walk induced signal noise has a divergent low frequency component, which is only rendered finite by the receptor adaptation process. For gradients within the E. coli sensing range, this dominant external noise can be comparable to the significant intrinsic noise in the system. The dependence of the response and its fluctuations on the key time scales of the system are studied systematically. We show that the chemotaxis pathway may have evolved to optimize gradient sensing, strong response, and noise control in different time scalesComment: 15 pages, 4 figure
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