«Systems Biology and Physiology Reports:Issue #3»
Опубликовано 30 сентября 2021
Hubs and Webs in Platelet Intracellular Signalling
In this issue of Systems Biology and Physiology Reports A.A. Martyanov and M.A. Panteleev suggested a review on platelet intracellular signalling network, which is a second part in the discussion on the molecular relationships between platelet activation and responses . The review contains seven thousands words and two hundred references and yet it is not complete, as there are still unclear parts in platelet signalling, especially in its inhibition [2-4]. In an effort to comprehend the platelet activation pattern, I drew a signalling scheme based on the review and data from other authors [2, 3].
Platelet functional responses and signalling: the molecular relationship. Part 2: receptors.
Small, non-nuclear cells, platelets, are primarily designed to form aggregates when blood vessels are damaged, stopping bleeding. To perform this function, platelets can implement several functional responses induced by various agonists and coordinated by a complex network of intracellular signaling triggered by a dozen of different receptors. This review, the second in a series, describes the known intracellular signaling pathways induced by platelet receptors in response to canonical and rare agonists. Particular focus will be on interaction points and “synergy” of platelet activation pathways and intermediate or “secondary” activation mediators that transmit a signal to functional manifestations.
A minimal mathematical model of neutrophil pseudopodium formation during chemotaxis
The directed movement of neutrophils is provided by the rapid polymerization of actin with the formation of a protrusion growing forward. In our previous work we observed impaired neutrophil movement for patients with Wiskott-Aldrich syndrome (WAS) compared to healthy donors.
In this work, we set out to explain the impairment of neutrophil chemotaxis in patients by observation and computer modeling of the linear growth rates of the anterior pseudopodia. The neutrophil chemotaxis was observed by means of low-angle fluorescent microscopy in parallel-plate flow chambers. The computational model was constructed as a network-like 2D stochastic polymerization of actin guided by the proximity of cell membrane with branching governed by Arp2/3 and WASP proteins.
The observed linear velocity of neutrophil pseudopodium formation was 0.22 ± 0.04 μm/s for healthy donors and 0.23 ± 0.08 μm/s for WAS patients. The model described the velocity of the pseudopodium formation for healthy donors well. For the description of WAS patients data, a variation of branching velocity (governed by WASP) by an order of magnitude was applied, which did not significantly alter the linear protrusion growth velocity.
We conclude that the proposed mathematical model of neutrophil pseudopodium formation could describe the experimental data well, but the data on overall neutrophil movement could not be explained by the velocities of the pseudopodium growth.
Overview of the neutralizing antibody and memory B cell response kinetics in SARS-CoV-2 convalescent and/or mRNA vaccinated individuals.
COVID-19 pandemics triggered by the SARS-CoV-2 virus have caused millions of deaths worldwide and have led to expedited developments of various effective vaccines that, if administered, could prevent and/or circumvent the infection and reduce the death toll. Since the start of the pandemics multiple research groups around the world have been involved in the analysis of immune responses of various human cohorts to the SARS-CoV-2 infection and vaccines. Now, over 1.5 years later, the scientific community has accumulated extensive data about both the development of an immune response to SARS-CoV-2 following infection, as well as its rate of fading off. Kinetic analysis of the immune response generated by vaccines is also emerging, enabling the possibility of making comparisons and predictions. In this review we will focus on the comparing B cell and antibody immune responses to the SARS-CoV-2 infection as opposed to mRNA vaccines for the SARS-CoV-2 S-protein, which have been utilized to immunize hundreds of millions of people and analyzed in multiple studies.