ProEnd: A Comprehensive Database for Identifying HbYX Motif-Containing Proteins Across the Tree of Life.

The proteasome plays a crucial role in cellular homeostasis by degrading misfolded, damaged, or unnecessary proteins. Understanding the regulatory mechanisms of proteasome activity is vital, particularly the interaction with activators containing the hydrophobic-tyrosine-any amino acid (HbYX) motif. Here, we present ProEnd, a comprehensive database designed to identify and catalog HbYX motif-containing proteins across the tree of life. Using a simple bioinformatics pipeline, we analyzed approximately 73 million proteins from 22,000 reference proteomes in the UniProt/SwissProt database. Our findings reveal the widespread presence of HbYX motifs in diverse organisms, highlighting their evolutionary conservation and functional significance. Notably, we observed an interesting prevalence of these motifs in viral proteomes, suggesting strategic interactions with the host proteasome. As validation two novel HbYX proteins found in this database were tested and found to directly interact with the proteasome. ProEnd's extensive dataset and user-friendly interface enable researchers to explore the potential proteasomal regulator landscape, generating new hypotheses to advance proteasome biology. This resource is set to facilitate the discovery of novel therapeutic targets, enhancing our approach to treating diseases such as neurodegenerative disorders and cancer. Link: http://proend.org/.

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.

From macroevolution's "independence proclamation" to the "act of independence". / Del "grito de independencia" de la macroevolución al "acto independentista"

J. Gould constantly argues against the Neodarwinian conception of macroevolution as a "reductionist and trivialized" perspective. Currently this conception is still prevalent; as can be noted on the conceptualization of macroevolutionary process, as just a mere gradualist interpolation of the microevolutionary process. The claims for the theoretical independence of the macroevolution, mainly exposed by Gould and Eldredge in what they call "the ontological maturation of biology", defending an ontological status of the hierarchical nature of biological organization, in opposition of a mere descriptive-epistemological scheme, were largely ignored or relegated as part of the philosophical problem of the units of selection. Perhaps, the absence of a convincing evolutionary mechanism or mode in the upper levels of the biological organization -as species-, that was non-reducible to the genetic level might explain the lack of interest of evolutionary biologist. However, current developments in the multilevel selection theory, as the concept of evolutionary transitions in individuality, together with symbiogenetic theory of evolution provides a better conceptualization of macroevolution, that might overcome the "claim" to the "act" of ontological independence. A re-conceptualization possible by the recognition of a non-reducible upper-level mode and tempo of evolution, in the sense of vertical evolutionary mechanisms or transitions of individuality by means of persistent symbiosis, as viral chronic-infections or any other symbiogenetic agent.

J. Gould criticó constantemente la concepción de la macroevolución por parte del neodarwinismo, como "reduccionista y trivializadora". No obstante, esta es la concepción vigente en la actualidad, como se evidencia en la conceptualización del proceso macorevolutivo, como interpolación gradualista de los procesos microevolutivos. Los gritos a favor de la independencia teórica de la macroevolución principalmente esgrimidos por Eldredge y Gould en lo que llamaron, la "maduración ontológica de la biología", reclamaban reconocer a la organización jerárquica biológica como esquema ontológico y no, como mero concepto descriptivo-epistemológico, fueron ignorados o relegados al interminable debate de la unidad de selección. Quizás, a razón de la ausencia de la identificación de un mecanismo o modo evolutivo convincente y propio de niveles de orden superior al nivel genético. Sin embargo, gracias a los desarrollos de la teoría de selección en múltiples niveles, como el concepto de transiciones evolutivas en individualidad, junto a la teoría simbiogenética de evolución, en el presente trabajo se plantea que una reconceptualización en el seno de dichos desarrollos permitiría avanzar del "grito" al "acto" independentista de la macroevolución. El carácter autónomo o la particularidad del tempo y modo residirían en mecanismos evolutivos verticales como las transiciones en individualidad mediadas por simbiosis persistentes, como las infecciones virales crónicas o por otros agentes simbiogenéticos.

Overthrow or extend Modern Synthesis? / ¿Revolucionar o actualizar la síntesis evolutiva moderna?

The pluralistic state of contemporary evolutionary theory has resulted into an academic confrontation, commonly exposed as a debate between two sides. On one side are those who defend synthetic theory of evolution (STE) can understand, translate and refute the evolutionary interpretations emerging from the new empirical and conceptual advance of current biological science. On the other side are those who claim the needs of a rethinking or a drastic conceptual change, or even considered a search for a new paradigm. In the present work I argue against the dual analysis of the debate, due to it is not able to capture the current epistemological pluralism of evolutionary biology, as an alternative I tried to collect and present such diversity of theories. The characterization proposed here is based on four epistemological attitudes towards TSE, called "Rejection", "Expansion", "Revolutionize" and "Formal re-foundation". Employing these attitudes is possible organize and group different theoretical and empirical frameworks, for instance the nongenetic inheritance theory, Niche construction theory along with others. The grouping criterion is based on the identification of common ontological assumptions and epistemological objectives. As the conception of the extension and intension of the inheritance concept. Whereas the dissimilarity in basic ontological notions, is proposed here as the main source of controversy and theoretical diversity.

El estado pluralista de la biología evolutiva contemporánea ha dado lugar a un enfrentamiento académico, comúnmente exhibido como una disputa entre dos grupos. Por una parte, se encuentran quienes consideran que la teoría sintética de la evolución (TSE) aún puede comprender, traducir o refutar las interpretaciones evolutivas que se desprenden de los nuevos avances empíricos y conceptuales de las ciencias biológicas. En oposición, están quienes consideran que la TSE requiereun cambio drástico de sus bases conceptuales o incluso debe ser rechazada a favor de una teoría alternativa. En el presente trabajo se exponen las razones por las que el análisis dual del debate niega la riqueza epistemológica actual, a su vez proponiendo una caracterización más apropiada, a partir de la categorización en cuatro actitudes epistemológicas frente a la TSE, denominadas "Abandonar", "Actualizar", "Revolucionar" y "Re-fundar". En dichas actitudes se logra organizar yagrupar diferentes marcos teóricos-empíricos, entre ellos las teorías de herencia no-genética, T. de la construcción del nicho, entre otros. La agrupación se realiza a partir de la identificación de presupuestos ontológicos comunes orientados hacia metas epistemológicas concretas, como la concepción sobre la extensión e intensión del concepto de herencia, como propuesta expansionista de la STE; mientras que la disimilitud en dichos presupuestos se propone como la fuente de controversia, que es a su vez, evidencia diversidad teórica.

Author Correction: Synergy between the anthocyanin and RDR6/SGS3/DCL4 siRNA pathways expose hidden features of Arabidopsis carbon metabolism.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Synergy between the anthocyanin and RDR6/SGS3/DCL4 siRNA pathways expose hidden features of Arabidopsis carbon metabolism.

Anthocyanin pigments furnish a powerful visual output of the stress and metabolic status of Arabidopsis thaliana plants. Essential for pigment accumulation is TRANSPARENT TESTA19 (TT19), a glutathione S-transferase proposed to bind and stabilize anthocyanins, participating in their vacuolar sequestration, a function conserved across the flowering plants. Here, we report the identification of genetic suppressors that result in anthocyanin accumulation in the absence of TT19. We show that mutations in RDR6, SGS3, or DCL4 suppress the anthocyanin defect of tt19 by pushing carbon towards flavonoid biosynthesis. This effect is not unique to tt19 and extends to at least one other anthocyanin pathway gene mutant. This synergy between mutations in components of the RDR6-SGS3-DCL4 siRNA system and the flavonoid pathway reveals genetic/epigenetic mechanisms regulating metabolic fluxes.

Dengue virus potentially promotes migratory responses on endothelial cells by enhancing pro-migratory soluble factors and miRNAs.

The most life-threatening effect of the Dengue virus (DENV) infection is an acute destabilization of the microvascular endothelial cell (MEC) barrier leading to plasma leakage, hypovolemic shock and haemorrhage. However, the underlying cellular mechanisms responsible for the dysfunction of MECs are not well understood. To identify potential cellular processes altered during DENV infection of MECs, expression profiles of cytokines/growth factors and microRNAs were measured by Luminex assay and next generation sequencing, respectively. Synchronously DENV2-infected MECs increase the secretion of IL-6, IL-8, FGF-2, GM-CSF, G-CSF, TGF-α, GRO, RANTES, MCP-1 and MCP-3. Conditioned media of infected MECs increased the migration of non-infected MECs. Furthermore, six miRNAs deregulated at 24 hpi were predicted to regulate host genes involved in cell migration and vascular developmental processes such as angiogenesis. These in silico analyses provide insights that support that DENV promotes an acute migratory phenotype in MECs that contributes to the vascular destabilization observed in severe dengue cases.