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«Systems Biology and Physiology Reports: Issue #1»

Опубликовано 31 марта 2021
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Platelet functional responses and signalling: the molecular relationship. Part 1: responses.

Blood platelets are small anucleated cells whose main function is to form a plug upon vascular damage to stop bleeding. This role involves a number of functional responses induced by different agonists and coordinated by an intricate network of signal transduction pathways. Understanding this network is vital from both basic research point of view and for the purposes of drug target identification in thrombosis and hemostasis. This review series will focus on the regulation of platelet signalling, on tracking the molecular relationship between receptor activation and functional responses, and on the networking aspects of these pathways. The present paper, first one out of two, focuses on the description of platelet functional responses and of the conditions for their triggering.
Platelet functional responses within arterial thrombus.
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#hemostasis#platelet activation#platelet intracellular signaling#thrombosis#thrombus formation

Avoiding common problems with statistical analysis of biological experiments using a simple nested data simulator

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Despite an extensive literature on statistical methods and their proper application to biological data, incorrect analyses remain a critical and widely spread problem in research papers. Inherently hierarchical (nested, clustered) structure of biological measurements is often erroneously neglected, leading to pseudo-replication and false positive results. This, in turn, complicates the correct assessment of statistical power and impairs optimal planning of experiments. In order to attract more attention to this problem and to illustrate the importance of direct account for the nested structure of biological data, in this article we present a simple open-source simulator of two-level normally distributed stochastic data. By defining ‘true’ mean values and ‘true’ intra- and inter-cluster variances of the simulated data, users of the simulator can test various scenarios, appreciate the importance of using correct multi-level analysis and the danger of neglecting the information about the data structure. Here we apply our nested data simulator to highlight some commonly arising mistakes with data analysis and propose a workflow, in which our simulator could be employed to correctly compare two nested groups of experimental data and to optimally plan new experiments in order to increase statistical power when necessary.
Schematic of a typical biological experiment design, generating nested data
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#nested data#statistical analysis#p-value#false positive#false negative#statistical power#simulated data#intra-cluster correlation

Patch-clamp technique for studying ion channels in activated platelets

In this study, we have revisited the existing and suggested new approaches to the use of patch-clamp methodology for measuring the activity of single ion channels and membrane potential of human platelets in the cell-attached configuration. We recorded single-channel events of platelets in the cell-attached configuration after activation with potent agonists: thrombin and ionomycin. The feasibility of platelet membrane potential measurement in cell-attached mode was investigated both experimentally and with the help of simple electrical circuits, revealing that the single-channel events can alter the recorded potential by invoking oscillations. Here, the simple approach to obtain inside-out configuration was described and calcium-dependent single-channel ion currents were recorded. Taken together, this study introduces new approaches for further investigations of the role of ion channels and membrane potential in platelet physiological and pathophysiological response.
Schematic illustration of recording currents of single ion channels of platelets during activation, excluding K<sub>v</sub> 1.3
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#platelets#patch-clamp#membrane potential#ion channel

Systems approaches meet biology and physiology: why do we need yet another journal?

Modern biological science in the past 50 years has made a spectacular journey providing us fascinating insights into the nature of living organisms and leading to accumulation of incredible amount of information. Nowadays, we observe introduction of the new systems approaches that allow us to supplement the qualitative nature of the life sciences by quantitative and mechanism-driven analysis. More and more scientists are becoming attracted by the unique opportunities that are provided by the novel synthetic approaches, encompassed by the systems biology, systems physiology and systems pharmacology in various fields. Right now, it is not simply mathematical or computational modelling of biological systems: a wide range of tools, including various approaches from big data field, progressive statistical methods, "omics" and others, are used to get insight into the mechanism of health and disease.
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