Toward a Categorization of Virus-ncRNA Interactions in the World of RNA to Disentangle the Tiny Secrets of Dengue Virus.

In recent years, the function of noncoding RNAs (ncRNAs) as regulatory molecules of cell physiology has begun to be better understood. Advances in viral molecular biology have shown that host ncRNAs, cellular factors, and virus-derived ncRNAs and their interplay are strongly disturbed during viral infections. Nevertheless, the folding of RNA virus genomes has also been identified as a critical factor in regulating canonical and non-canonical functions. Due to the influence of host ncRNAs and the structure of RNA viral genomes, complex molecular and cellular processes in infections are modulated. We propose three main categories to organize the current information about RNA-RNA interactions in some well-known human viruses. The first category shows examples of host ncRNAs associated with the immune response triggered in viral infections. Even though miRNAs introduce a standpoint, they are briefly presented to keep researchers moving forward in uncovering other RNAs. The second category outlines interactions between virus-host ncRNAs, while the third describes how the structure of the RNA viral genome serves as a scaffold for processing virus-derived RNAs. Our grouping may provide a comprehensive framework to classify ncRNA-host-cell interactions for emerging viruses and diseases. In this sense, we introduced them to organize DENV-host-cell interactions.

We know that we don't know: Children's understanding of common ignorance in a coordination game.

Common ground is the knowledge, beliefs, and suppositions shared between partners in an interaction. Previous research has focused extensively on what partners know they know together, that is, "common knowledge." However, another important aspect of common ground is what partners know they do not know together, that is, "common ignorance." A new coordination game was designed to investigate children's use of common ignorance. Without communicating or seeing each other's decisions, 4- to 8-year-olds needed to make the same decision as their partner about whether to try to retrieve a reward. To retrieve it, at least one of them needed to know a secret code. The knowledge/ignorance of both partners was ostensively manipulated by showing one partner, both partners, or neither partner the secret code in four conditions: common knowledge (both knew the code), common ignorance (neither partner knew the code), common privileged self knowledge (only children knew the code), and common privileged other knowledge (only their partner knew the code). Children's decisions, latency, and uncertainty were coded. Results showed that the common ignorance states were generally more difficult than the common knowledge states. Unexpectedly, children at all ages had difficulty with coordinating when their partner knew the code but they themselves did not (common privileged other knowledge). This study shows that, along with common knowledge, common ignorance and common privileged self knowledge and other knowledge also play important roles in coordinating with others but may develop differently.

A predator-prey fractional model with disease in the prey species.

In this paper, we study a generalized eco-epidemiological model of fractional order for the predator-prey type in the presence of an infectious disease in the prey. The proposed model considers that the disease infects the prey, causing them to be divided into two classes, susceptible prey and infected prey, with different density-dependent predation rates between the two classes. We propose logistic growth in both the prey and predator populations, and we also propose that the predators have alternative food sources (i.e., they do not feed exclusively on these prey). The model is evaluated from the perspective of the global and local generalized derivatives by using the generalized Caputo derivative and the generalized conformable derivative. The existence, uniqueness, non-negativity, and boundedness of the solutions of fractional order systems are demonstrated for the classical Caputo derivative. In addition, we study the stability of the equilibrium points of the model and the asymptotic behavior of its solution by using the Routh-Hurwitz stability criteria and the Matignon condition. Numerical simulations of the system are presented for both approaches (the classical Caputo derivative and the conformable Khalil derivative), and the results are compared with those obtained from the model with integro-differential equations. Finally, it is shown numerically that the introduction of a predator population in a susceptible-infectious system can help to control the spread of an infectious disease in the susceptible and infected prey population.

Systematic computational hunting for small RNAs derived from ncRNAs during dengue virus infection in endothelial HMEC-1 cells.

In recent years, a population of small RNA fragments derived from non-coding RNAs (sfd-RNAs) has gained significant interest due to its functional and structural resemblance to miRNAs, adding another level of complexity to our comprehension of small-RNA-mediated gene regulation. Despite this, scientists need more tools to test the differential expression of sfd-RNAs since the current methods to detect miRNAs may not be directly applied to them. The primary reasons are the lack of accurate small RNA and ncRNA annotation, the multi-mapping read (MMR) placement, and the multicopy nature of ncRNAs in the human genome. To solve these issues, a methodology that allows the detection of differentially expressed sfd-RNAs, including canonical miRNAs, by using an integrated copy-number-corrected ncRNA annotation was implemented. This approach was coupled with sixteen different computational strategies composed of combinations of four aligners and four normalization methods to provide a rank-order of prediction for each differentially expressed sfd-RNA. By systematically addressing the three main problems, we could detect differentially expressed miRNAs and sfd-RNAs in dengue virus-infected human dermal microvascular endothelial cells. Although more biological evaluations are required, two molecular targets of the hsa-mir-103a and hsa-mir-494 (CDK5 and PI3/AKT) appear relevant for dengue virus (DENV) infections. Here, we performed a comprehensive annotation and differential expression analysis, which can be applied in other studies addressing the role of small fragment RNA populations derived from ncRNAs in virus infection.

Selection of software agile practices using Analytic hierarchy process.

Context: The increasing use of software and information technology in modern society requires that the deployment of IT solutions should be more efficient and controlled. In this sense, agile methodologies are essential to achieve this goal, but a relevant question arises: Which is the right methodology for reaching that goal? Objective: The purpose of the research was to study the prioritization of agile practices and improvement objectives in the context of software development, using the Analytic Hierarchy Process (AHP) method. For this purpose, 42 agile practices, 16 improvement objectives, 4 organizations dedicated to software development in Colombia and 40 professionals in the area of information and communication technologies in the same country were considered. Method: ology: The methodological approach used was mixed. On the one hand, we applied a quantitative approach for the treatment of data with the AHP method and, on the other hand, a qualitative analysis by consulting experts through a digital survey to validate the prioritization of the improvement objectives. Questionpro was used as a support tool for multicriteria comparison. Results: The main results show that applying AHP allowed us to prioritize 6 improvement objectives and 5 agile practices, where it is highlighted that the prioritization does not discard the other objects of comparison but allows us to put into practice the prioritized elements to favor their progressive implementation. The non-prioritized elements could be part of future iterations of multicriteria comparison that go hand in hand with capacity development and organizational maturity models in the context of global software development. Conclusion: It is highlighted that, although there is evidence of the application of multi-criteria comparison methods in the software development industry, this work applies such methods in the context of four different agile methodologies, which translates into a precedent for the conformation of hybrid methodological approaches.

Correction: Escudero-Flórez et al. Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial-Mesenchymal-Transition-like Changes in Human Microvascular Endothelial Cells. Viruses 2023, 15, 1437.

Ryan L [...].

Telepsychiatry: The future is already present.

This review paper analyzes the state of knowledge on Telepsychiatry (TP) after the crisis caused by COVID and the resulting need to use new modalities of care. Six essential aspects of TP are addressed: patient's and mental health staff satisfaction, diagnostic reliability, effectiveness of TP interventions, cost-effectiveness in terms of opportunity cost (or efficiency), legal aspects inherent to confidentiality and privacy in particular and the attitude of professionals toward TP. Satisfaction with TP is acceptable among both patients and professionals, the latter being the most reluctant. Diagnostic reliability has been demonstrated, but requires further studies to confirm this reliability in different diagnoses and healthcare settings. The efficacy of TP treatments is not inferior to face-to-face care, as has been proven in specific psychotherapies. Finally, it should be noted that the attitude of the psychiatrist is the most decisive element that limits or facilitates the implementation of TP.

Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial-Mesenchymal-Transition-Like Changes in Human Microvascular Endothelial Cells.

Dengue virus (DENV) is a pathogenic arbovirus that causes human disease. The most severe stage of the disease (severe dengue) is characterized by vascular leakage, hypovolemic shock, and organ failure. Endothelial dysfunction underlies these phenomena, but the causal mechanisms of endothelial dysfunction are poorly characterized. This study investigated the role of c-ABL kinase in DENV-induced endothelial dysfunction. Silencing c-ABL with artificial miRNA or targeting its catalytic activity with imatinib revealed that c-ABL is required for the early steps of DENV infection. DENV-2 infection and conditioned media from DENV-infected cells increased endothelial expression of c-ABL and CRKII phosphorylation, promoted expression of mesenchymal markers, e.g., vimentin and N-cadherin, and decreased the levels of endothelial-specific proteins, e.g., VE-cadherin and ZO-1. These effects were reverted by silencing or inhibiting c-ABL. As part of the acquisition of a mesenchymal phenotype, DENV infection and treatment with conditioned media from DENV-infected cells increased endothelial cell motility in a c-ABL-dependent manner. In conclusion, DENV infection promotes a c-ABL-dependent endothelial phenotypic change that leads to the loss of intercellular junctions and acquisition of motility.

A new host-targeted antiviral cyclolignan (SAU-22.107) for Dengue Virus infection in cell cultures. Potential action mechanisms based on cell imaging.

Dengue virus (DENV) infection is the most arbovirosis in the world. However, medications have not been approved for its treatment. Drug discovery based on the host-targeted antiviral (HTA) constitutes a new promising strategy, considering their high genetic barrier to resistance and the low probability of selecting drug resistance strains. In this study, we have tested fifty-seven podophyllotoxin-related cyclolignans on DENV-2 infected cells and found the most promising compound was S.71. Using cellular and molecular biology experiments, we have discovered that the new lignan altered the distribution of microtubules, induced changes in cell morphology, and caused retraction of the rough endoplasmic reticulum. In addition, the compound alters the viral envelope protein and the double-stranded RNA, while there is a decrease in negative-strand RNA synthesis; especially when the compound was added between 6- and 12-hours post-infection. Altogether, S.71 decreases the viral yield through an HTA-related mechanism of action, possibly altering the DENV genome replication and/or polyprotein translation, through the alteration of microtubule distribution and endoplasmic reticulum deterioration. Finally, pharmacokinetic predictors show that S.71 falls within the standard ranges established for drugs.