Modelling quarantine effects on SARS-CoV-2 epidemiological dynamics in Chilean communes and their relationship with the Social Priority Index.

Background: An epidemiological model (susceptible, un-quarantined infected, quarantined infected, confirmed infected (SUQC)) was previously developed and applied to incorporate quarantine measures and calculate COVID-19 contagion dynamics and pandemic control in some Chinese regions. Here, we generalized this model to incorporate the disease recovery rate and applied our model to records of the total number of confirmed cases of people infected with the SARS-CoV-2 virus in some Chilean communes. Methods: In each commune, two consecutive stages were considered: a stage without quarantine and an immediately subsequent quarantine stage imposed by the Ministry of Health. To adjust the model, typical epidemiological parameters were determined, such as the confirmation rate and the quarantine rate. The latter allowed us to calculate the reproduction number. Results: The mathematical model adequately reproduced the data, indicating a higher quarantine rate when quarantine was imposed by the health authority, with a corresponding decrease in the reproduction number of the virus down to values that prevent or decrease its exponential spread. In general, during this second stage, the communes with the lowest social priority indices had the highest quarantine rates, and therefore, the lowest effective viral reproduction numbers. This study provides useful evidence to address the health inequity of pandemics. The mathematical model applied here can be used in other regions or easily modified for other cases of infectious disease control by quarantine.

Search for Novel Potent Inhibitors of the SARS-CoV-2 Papain-like Enzyme: A Computational Biochemistry Approach.

The rapid emergence and spread of new variants of coronavirus type 2, as well as the emergence of zoonotic viruses, highlights the need for methodologies that contribute to the search for new pharmacological treatments. In the present work, we searched for new SARS-CoV-2 papain-like protease inhibitors in the PubChem database, which has more than 100 million compounds. Based on the ligand efficacy index obtained by molecular docking, 500 compounds with higher affinity than another experimentally tested inhibitor were selected. Finally, the seven compounds with ADME parameters within the acceptable range for such a drug were selected. Next, molecular dynamics simulation studies at 200 ns, ΔG calculations using molecular mechanics with generalized Born and surface solvation, and quantum mechanical calculations were performed with the selected compounds. Using this in silico protocol, seven papain-like protease inhibitors are proposed: three compounds with similar free energy (D28, D04, and D59) and three compounds with higher binding free energy (D60, D99, and D06) than the experimentally tested inhibitor, plus one compound (D24) that could bind to the ubiquitin-binding region and reduce the effect on the host immune system. The proposed compounds could be used in in vitro assays, and the described protocol could be used for smart drug design.

Iba57p participates in maturation of a [2Fe-2S]-cluster Rieske protein and in formation of supercomplexes III/IV of Saccharomyces cerevisiae electron transport chain.

The [Fe-S] late-acting subsystem comprised of Isa1p/Isa2p, Grx5p, and Iba57p proteins (Fe-S-IBG subsystem) is involved in [4Fe-4S]-cluster protein assembly. The effect of deleting IBA57 in Saccharomyces cerevisiae on mitochondrial respiratory complex integration and functionality associated with Rieske protein maturation was evaluated. The iba57Δ mutant showed decreased expression and maturation of the Rieske protein. The loss of Rieske protein caused by IBA57 deletion affected the structure of supercomplexes III2IV2 and III2IV1 and their integration into the mitochondria, causing dysfunction in the electron transport chain. These effects were correlated with decreased cytochrome functionality and content in the iba57Δ mutant. These findings suggest that Iba57p participates in maturation of the [2Fe-2S]-cluster into the Rieske protein and that Rieske protein plays important roles in the conformation and functionality of mitochondrial supercomplex III/IV in the electron transport chain.

Data on the role of iba57p in free Fe2+ release and O2∙- generation in Saccharomyces cerevisiae.

The related study has confirmed that in Saccharomyces cerevisiae, iba57 protein participates in maturation of the [2Fe-2S] cluster into the Rieske protein, which plays important roles in the conformation and functionality of mitochondrial supercomplexes III/IV in the electron transport chain (Sánchez et al., 2018) [1]. We determined in S. cerevisiae the effects of mutation in the IBA57 gene on reactive oxygen species (ROS) and iron homeostasis. Flow cytometry and confocal microscopy analyses showed an increased generation of ROS, correlated with free Fe2+ release in the IBA57 mutant yeast. Data obtained support that a dysfunction in the Rieske protein has close relationship between ROS generation and free Fe2+ content, and which is possible that free Fe2+ release mainly proceeds from [Fe-S] cluster-containing proteins.

Inequality of opportunity in health: evidence from Chile.

OBJECTIVE: To assess the possible presence of inequality of opportunities in the health status of Chileans, according to sociodemographic circumstances. METHODS: Self-rated health data were used from the Chilean National Health Survey of 2010 to test the hypothesis of strong and weak equality of opportunities in the health status of the Chilean population. These hypotheses were tested using nonparametric techniques and second-order stochastic dominance criteria. RESULTS: Robust empirical evidence was obtained, which indicate that the education level of the mother, household socioeconomic status, sex, zone, and region of residence determine opportunities to achieve good health in Chile. CONCLUSIONS: Better health status was identified for Chilean adults whenever their mothers had a higher education level, their household income was higher, they were men, or lived in urban areas. The region of residence also affects opportunities to achieve good health in Chile.

Inequality of opportunity in health: evidence from Chile

ABSTRACT OBJECTIVE To assess the possible presence of inequality of opportunities in the health status of Chileans, according to sociodemographic circumstances. METHODS Self-rated health data were used from the Chilean National Health Survey of 2010 to test the hypothesis of strong and weak equality of opportunities in the health status of the Chilean population. These hypotheses were tested using nonparametric techniques and second-order stochastic dominance criteria. RESULTS Robust empirical evidence was obtained, which indicate that the education level of the mother, household socioeconomic status, sex, zone, and region of residence determine opportunities to achieve good health in Chile. CONCLUSIONS Better health status was identified for Chilean adults whenever their mothers had a higher education level, their household income was higher, they were men, or lived in urban areas. The region of residence also affects opportunities to achieve good health in Chile.

Local conditions for global stability in the space of codons of the genetic code.

The polar requirement is an attribute of amino acids that is a major determinant of the structure and function of the proteins, and it plays a role in the flexibility and robustness of the genetic code. The viability of an organism depends on flexibility, which allows the exploration of new functions. However, robustness is necessary to protect the organism from deleterious changes derived from misreading errors and single-point mutations. Compared with random codes, the standard genetic code is one of the most robust against such errors. Here, using analytical and numerical calculations and the set of amino acid-encoding codons, we have proposed some local conditions that are necessary for the optimal robustness of the genetic code, and we explored the association between the local conditions and the robustness. The localness of the proposed conditions and the underlying evolutionary mechanism, which begins with a random code and progresses toward more efficient codes (e.g., the standard code), might be biologically plausible.

Probable relationship between partitions of the set of codons and the origin of the genetic code.

Here we study the distribution of randomly generated partitions of the set of amino acid-coding codons. Some results are an application from a previous work, about the Stirling numbers of the second kind and triplet codes, both to the cases of triplet codes having four stop codons, as in mammalian mitochondrial genetic code, and hypothetical doublet codes. Extending previous results, in this work it is found that the most probable number of blocks of synonymous codons, in a genetic code, is similar to the number of amino acids when there are four stop codons, as well as it could be for a primigenious doublet code. Also it is studied the integer partitions associated to patterns of synonymous codons and it is shown, for the canonical code, that the standard deviation inside an integer partition is one of the most probable. We think that, in some early epoch, the genetic code might have had a maximum of the disorder or entropy, independent of the assignment between codons and amino acids, reaching a state similar to "code freeze" proposed by Francis Crick. In later stages, maybe deterministic rules have reassigned codons to amino acids, forming the natural codes, such as the canonical code, but keeping the numerical features describing the set partitions and the integer partitions, like a "fossil numbers"; both kinds of partitions about the set of amino acid-coding codons.

The most probable number of blocks for the partitions of the set of codons could have determined the number of standard amino acids.

Given a genetic code formed by 64 codons, we calculate the number of partitions of the set of encoding amino acid codons. When there are 0-3 stop codons, the results indicate that the most probable number of partitions is 19 and/or 20. Then, assuming that in the early evolution the genetic code could have had random variations, we suggest that the most probable number of partitions of the set of encoding amino acid codons determined the actual number 20 of standard amino acids.