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Register a new userVaccination pattern affects immunological response
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P. Etchegoin
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The response of the immune system to different vaccination patterns is studied with a simple model. It is argued that the history and characteristics of the pattern defines very different secondary immune responses in the case of infection. The memory function of the immune response can be set to work in very different modes depending on the pattern followed during immunizations. It is argued that the history and pattern of immunizations can be a decisive (and experimentally accessible) factor to tailor the effectiveness of a specific vaccine.
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Gene expression is a noisy process and several mechanisms, both transcriptional and posttranscriptional, can stabilize protein levels in cells. Much work has focused on the role of miRNAs, showing in particular that miRNA-mediated regulation can buffer expression noise for lowly expressed genes. Here, using in silico simulations and mathematical modeling, we demonstrate that miRNAs can exert a much broader influence on protein levels by orchestrating competition-induced crosstalk between mRNAs. Most notably, we find that miRNA-mediated cross-talk (i) can stabilize protein levels across the full range of gene expression rates, and (ii) modifies the correlation pattern of co-regulated interacting proteins, changing the sign of correlations from negative to positive. The latter feature may constitute a potentially robust signature of the existence of RNA crosstalk induced by endogenous competition for miRNAs in standard cellular conditions.
This work is a study of the inter-relationship between parameters that principally affect metal up-take in the plant. The relationships between the concentration of metal in the growth medium, Cs, the concentration of metal absorbed by the plant, Cp, and the total biomass achieved, M, all of which are factors relevant to the efficiency of phytoremediation of the plant, have been investigated via the macro-physiological response of Brassica juncea seedlings to Ni(II) stress. The factorial growth experiments treated the Ni(II) concentration in the agar gel and the diurnal light quanta (DLQ) as independently variable parameters. Observations included the evidence of light enhancement of Ni toxicity at the root as well as at the whole plant level, the shoot mass index as a possible indicator of shoot metal sequestration in B. juncea, the logarithmic variation of Cp with Cs and the power-law dependence of M on Cp. The sum total of these observations indicate that for the metal accumulator B. juncea with regard to its capacity to accumulate Ni, the overall metabolic nature of the plant is important; neither rapid biomass increase nor a high metal concentration capability favor the removal of high metal mass from the medium, but rather the plant with the moderate photosynthetically driven biomass growth and moderate metal concentrations demonstrated the ability to remove the maximum mass of metal from the medium. The implications of these observations in the context of the perceived need in phytoremediation engineering to maximize Cp and M simultaneously in the same plant, are discussed.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a variable clinical presentation that ranges from asymptomatic, to severe disease with cytokine storm. The mortality rates also differ across the globe, ranging from 0.5-13%. This variation is likely due to both pathogen and host factors. Host factors may include genetic differences in the immune response genes as well as variation in HLA and KIR allotypes. To better understand what impact these genetic variants in immune response genes may have in the differences observed in the immune response to SARS-CoV-2, a quantitative analysis of a dynamical systems model that considers both, the magnitude of viral growth, and the subsequent innate and adaptive response required to achieve control of infection is considered. Based on this broad quantitative framework it may be posited that the spectrum of symptomatic to severely symptomatic presentations of COVID19 represents the balance between innate and adaptive immune responses. In asymptomatic patients, prompt and adequate adaptive immune response quells infection, whereas in those with severe symptoms a slower inadequate adaptive response leads to a runaway cytokine cascade fueled by ongoing viral replication. Polymorphisms in the various components of the innate and adaptive immune response may cause altered immune response kinetics that would result in variable severity of illness. Understanding how this genetic variation may alter the response to SARS-CoV-2 infection is critical to develop successful treatment strategies.
The Coronavirus 2019 (Covid-19) pandemic caused by the SARS-CoV-2 virus represents an unprecedented crisis for our planet. It is a bane of the uber connected world that we live in that this virus has affected almost all countries and caused mortality and economic upheaval at a scale whose effects are going to be felt for generations to come. While we can all be buoyed at the pace at which vaccines have been developed and brought to market, there are still challenges ahead for all countries to get their populations vaccinated equitably and effectively. This paper provides an overview of ongoing immunization efforts in various countries. In this early draft, we have identified a few key factors that we use to review different countries current COVID-19 immunization strategies and their strengths and draw conclusions so that policymakers worldwide can learn from them. Our paper focuses on processes related to vaccine approval, allocation and prioritization, distribution strategies, population to vaccine ratio, vaccination governance, accessibility and use of digital solutions, and government policies. The statistics and numbers are dated as per the draft date [June 24th, 2021].
The Hill coefficient is often used as a direct measure of the cooperativity of binding processes. It is an essential tool for probing properties of reactions in many biochemical systems. Here we analyze existing experimental data and demonstrate that the Hill coefficient characterizing the binding of transcription factors to their cognate sites can in fact be larger than one -- the standard indication of cooperativity -- even in the absence of any standard cooperative binding mechanism. By studying the problem analytically, we demonstrate that this effect occurs due to the disordered binding energy of the transcription factor to the DNA molecule and the steric interactions between the different copies of the transcription factor. We show that the enhanced Hill coefficient implies a significant reduction in the number of copies of the transcription factors which is needed to occupy a cognate site and, in many cases, can explain existing estimates for numbers of the transcription factors in cells. The mechanism is general and should be applicable to other biological recognition processes.
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