: The new COVID-19 presents some comorbidities, such as obesity, Alzheimer’s, and coronary risk, ... more : The new COVID-19 presents some comorbidities, such as obesity, Alzheimer’s, and coronary risk, among others. We argue that the current understanding of some of these clinical conditions may illuminate the design of future COVID-19 studies to account for a bias that may be the cause of the paradoxical associations between COVID-19 mortality and cytokine storm. Given that we know some of the genetic mechanisms behind these diseases, it is possible to circumscribe these studies to some key genes that help us understand why some patients experience a cytokine storm and what the treatment strategies might be. In this paper, we discuss the role of A2M and APOE genes. A2M encodes a multifaceted protein which is highly expressed in the liver and released to the bloodstream associated with the apolipoprotein E. This association depends on the APOE genotype. A2M has protease-clearing activity binding of a broad range of proteases, such as thrombin and Factor Xa. It also presents the ability to bind to proinflammatory ligands, like cytokines. Further, A2M acts as chaperone of misfolded substrates, like betaamyloid peptide. The last two molecular functions grant it a key role in regulating both inflammatory processes, as well as extracellular protein homeostasis. For these reasons, we conclude that A2M-APOE association will have prophylactic, therapeutic, and prognostic implications; and the proper understanding of the physiological role of APOE and A2M in controlling inflammatory processes can shed further light on the putative treatment of COVID-19-derived cytokine storm.
Motivation Codon usage preference patterns have been associated with modulation of translation ef... more Motivation Codon usage preference patterns have been associated with modulation of translation efficiency, protein folding, and mRNA decay. However, new studies support that codon pair usage has also a remarkable effect at the gene expression level. Here, we expand the concept of CAI to answer if codon pair usage patterns can be understood in terms of codon usage bias, or if they offer new information regarding coding translation efficiency. Results Through the implementation of a weighting strategy to consider the dicodon contributions, we observe that the dicodon-based measure has greater correlations with gene expression level than CAI. Interestingly, we have noted that dicodons associated with a low value of adaptiveness are related to dicodons which mediate strong translational inhibition in yeast. We have also noticed that some codon-pairs have a smaller dicodon contribution than estimated by the product of the respective codon contributions. Availability and implementation Sc...
<p>Peak frequency (panel A) and the quality factor <i>Q</i><sub>90%</s... more <p>Peak frequency (panel A) and the quality factor <i>Q</i><sub>90%</sub> (panel B) as a function of <i>ϵ</i> and <i>λ</i>, for oscillations in the number fluctuations of repressor for the same parameter than <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151086#pone.0151086.g004" target="_blank">Fig 4</a>, but with <i>N</i> = 5 instead of <i>N</i> = 3.</p
One of the most surprising mechanisms to explain the symmetry breaking phenomenon linked to patte... more One of the most surprising mechanisms to explain the symmetry breaking phenomenon linked to pattern formation is known as Turing instabilities. These patterns are self-organising spatial structures resulting from the interaction of at least two diffusive species in specific conditions. The ideas of Turing have been used extensively in the specialised literature both to explain developmental patterns, as well as synthetic biology design. In the present work we study a previously proposed morphogenetic synthetic circuit consisting of two genes controlled by the same regulatory system. The spatial homogeneous version of this simple model presents a rich phase diagram, since it has a saddle-node bifurcation, spirals and limit cycle. Linear stability analysis and numerical simulations of the complete model allow us to determine the conditions for the development of Turing patterns, as well as transient patterns. We found that the parameter region where Turing patterns are found is much s...
: The new COVID-19 presents some comorbidities, such as obesity, Alzheimer’s, and coronary risk, ... more : The new COVID-19 presents some comorbidities, such as obesity, Alzheimer’s, and coronary risk, among others. We argue that the current understanding of some of these clinical conditions may illuminate the design of future COVID-19 studies to account for a bias that may be the cause of the paradoxical associations between COVID-19 mortality and cytokine storm. Given that we know some of the genetic mechanisms behind these diseases, it is possible to circumscribe these studies to some key genes that help us understand why some patients experience a cytokine storm and what the treatment strategies might be. In this paper, we discuss the role of A2M and APOE genes. A2M encodes a multifaceted protein which is highly expressed in the liver and released to the bloodstream associated with the apolipoprotein E. This association depends on the APOE genotype. A2M has protease-clearing activity binding of a broad range of proteases, such as thrombin and Factor Xa. It also presents the ability to bind to proinflammatory ligands, like cytokines. Further, A2M acts as chaperone of misfolded substrates, like betaamyloid peptide. The last two molecular functions grant it a key role in regulating both inflammatory processes, as well as extracellular protein homeostasis. For these reasons, we conclude that A2M-APOE association will have prophylactic, therapeutic, and prognostic implications; and the proper understanding of the physiological role of APOE and A2M in controlling inflammatory processes can shed further light on the putative treatment of COVID-19-derived cytokine storm.
Motivation Codon usage preference patterns have been associated with modulation of translation ef... more Motivation Codon usage preference patterns have been associated with modulation of translation efficiency, protein folding, and mRNA decay. However, new studies support that codon pair usage has also a remarkable effect at the gene expression level. Here, we expand the concept of CAI to answer if codon pair usage patterns can be understood in terms of codon usage bias, or if they offer new information regarding coding translation efficiency. Results Through the implementation of a weighting strategy to consider the dicodon contributions, we observe that the dicodon-based measure has greater correlations with gene expression level than CAI. Interestingly, we have noted that dicodons associated with a low value of adaptiveness are related to dicodons which mediate strong translational inhibition in yeast. We have also noticed that some codon-pairs have a smaller dicodon contribution than estimated by the product of the respective codon contributions. Availability and implementation Sc...
<p>Peak frequency (panel A) and the quality factor <i>Q</i><sub>90%</s... more <p>Peak frequency (panel A) and the quality factor <i>Q</i><sub>90%</sub> (panel B) as a function of <i>ϵ</i> and <i>λ</i>, for oscillations in the number fluctuations of repressor for the same parameter than <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151086#pone.0151086.g004" target="_blank">Fig 4</a>, but with <i>N</i> = 5 instead of <i>N</i> = 3.</p
One of the most surprising mechanisms to explain the symmetry breaking phenomenon linked to patte... more One of the most surprising mechanisms to explain the symmetry breaking phenomenon linked to pattern formation is known as Turing instabilities. These patterns are self-organising spatial structures resulting from the interaction of at least two diffusive species in specific conditions. The ideas of Turing have been used extensively in the specialised literature both to explain developmental patterns, as well as synthetic biology design. In the present work we study a previously proposed morphogenetic synthetic circuit consisting of two genes controlled by the same regulatory system. The spatial homogeneous version of this simple model presents a rich phase diagram, since it has a saddle-node bifurcation, spirals and limit cycle. Linear stability analysis and numerical simulations of the complete model allow us to determine the conditions for the development of Turing patterns, as well as transient patterns. We found that the parameter region where Turing patterns are found is much s...
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Papers by Luis Diambra