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Identification of master regulator genes controlling pathogenic CD4+ T cell fate in inflammatory bowel disease through transcriptional network analysis
Get PDFInflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions of the gastrointestinal tract associated with multiple pathogenic factors, including dysregulation of the immune response. Effector CD4+ T cells and regulatory CD4+ T cells (Treg) are central players in maintaining the balance between tolerance and inflammation. Interestingly, genetic modifications in these cells have been implicated in regulating the commitment of specific phenotypes and immune functions. However, the transcriptional program controlling the pathogenic behavior of T helper cells in IBD progression is still unknown. In this study, we aimed to find master transcription regulators controlling the pathogenic behavior of effector CD4+ T cells upon gut inflammation. To achieve this goal, we used an animal model of IBD induced by the transfer of naïve CD4+ T cells into recombination-activating gene 1 (Rag1) deficient mice, which are devoid of lymphocytes. As a control, a group of Rag1−/− mice received the transfer of the whole CD4+ T cells population, which includes both effector T cells and Treg. When gut inflammation progressed, we isolated CD4+ T cells from the colonic lamina propria and spleen tissue, and performed bulk RNA-seq. We identified differentially up- and down-regulated genes by comparing samples from both experimental groups. We found 532 differentially expressed genes (DEGs) in the colon and 30 DEGs in the spleen, mostly related to Th1 response, leukocyte migration, and response to cytokines in lamina propria T-cells. We integrated these data into Gene Regulatory Networks to identify Master Regulators, identifying four up-regulated master gene regulators (Lef1, Dnmt1, Mybl2, and Jup) and only one down-regulated master regulator (Foxo3). The altered expression of master regulators observed in the transcriptomic analysis was confirmed by qRT-PCR analysis and found an up-regulation of Lef1 and Mybl2, but without differences on Dnmt1, Jup, and Foxo3. These two master regulators have been involved in T cells function and cell cycle progression, respectively. We identified two master regulator genes associated with the pathogenic behavior of effector CD4+ T cells in an animal model of IBD. These findings provide two new potential molecular targets for treating IBD
Genetic population structure of lane snapper Lutjanus synagris (Linnaeus, 1758) in Western Atlantic: Implications for conservation
Get PDFGenetic structure and connectivity information can be used to identify biological corridors and prioritize the conservation of areas that help maintain ecosystem integrity. Some marine fish, especially those of commercial interest, have been proposed as suitable indicators to identify potential marine biological corridors due to their high mobility among habitats and socioeconomic importance. In this study, we assessed the genetic structure of lane snapper populations in the Honduran Caribbean to evaluate connectivity and identify potential environmental barriers. Furthermore, we evaluated the genetic characteristics of the lane snapper on a larger spatial scale, including populations across the rest of its distribution range in the western Atlantic, using mtDNA and nuDNA markers. Our results demonstrate a significant genetic diversity of lane snappers in the Honduran Caribbean. Furthermore, despite their high dispersal potential, we observed genetic structuring in lane snapper populations on a larger spatial scale, resulting in the formation of two distinct groups throughout their distribution range: group 1 from Florida, the Gulf of Mexico, Honduras, and Colombia and group 2 from Puerto Rico and Brazil. This genetic differentiation can be attributed to oceanographic barriers such as river plumes and marine currents. These findings have the potential to significantly impact marine conservation and management efforts in the region, both at local and regional scales. It is anticipated that they will not only inform but also elicit a response, driving further action towards effective conservation measures. At a local scale, we recommend that conservation efforts focus on protecting critical habitats. At a regional scale, lane snappers should be included in the management plans of existing marine protected areas necessary to ensure the long-term sustainability of the species and the marine ecosystems in which it resides
Estudios sobre propiedad intelectual, nuevas tecnologías y cosas incorporales. Miradas desde distintas ramas del Derecho
No full textLa presente obra colectiva, coeditada por la Facultad de Derecho de la Universidad Católica de la Santísima Concepción, Chile, da cuenta de cambios jurídicos y tecnológicos en el mundo actual, y de la evolución de la siempre interesante interacción entre Derecho y tecnología. El Derecho regula los avances tecnológicos, pero también se vale de ellos.
Con distintas miradas desde el Derecho de propiedad intelectual, Derecho del trabajo, Derecho civil, Derecho administrativo y Derecho procesal se analizan los fenómenos sociales y culturales asociados a los progresos de la tecnología y al auge de las cosas incorporales, bienes inmateriales y activos intangibles
Perception of hypotheticality in technology-based business ideas: effects on Opportunity Beliefs from a Construal Level Theory perspective
Get PDFThis research investigates how entrepreneurs perceive the hypothetical nature of technologies (based on situations that are often imagined or theoretical) as a foundation for entrepreneurial endeavors and how this perception influences the formation of business Opportunity Beliefs. Drawing on the Construal Level Theory, we explore the relationship between the perceived hypotheticality of technologies and Opportunity Beliefs. Two experimental studies are conducted to examine these relationships, with Study 1 (n = 177 entrepreneurs) focusing on the perception of innovative technologies as more distant or hypothetical, and Study 2 (n = 404 entrepreneurs) delving into how the perceived distance to technology influences Opportunity Beliefs. The results indicate that entrepreneurs view more innovative technologies as more hypothetical and that hypotheticality mediates the relationship between the perceived degree of innovation and Opportunity Beliefs. We find evidence that Entrepreneurs tend to view the feasibility and fit/alignment of business opportunities more favorably when they perceive the psychological distance (hypotheticality) of the opportunity as closer rather than more distant. However, the difference this difference is nonsignificant in how they evaluate the desirability of the opportunity in any psychological distance. These results provide insight into the cognitive processes of entrepreneurs and offer implications for understanding how entrepreneurs perceive and evaluate business opportunities
The physical and mechanical consequences of incorporating industrial residues into mortar and concrete mixtures for eco-friendly marine constructions
No full textIn pursuit of a more sustainable construction material with the potential to improve bioreceptivity in marine environments, this study investigates the feasibility of incorporating three industrial residues—steel sludge (“Conox”), mytilid mussel shells, and wheat straw fibers—as partial substitutes for cement and sand. The research focuses on evaluating the physical and mechanical properties of mortar and concrete mixtures containing these residues, both individually and in combination. Additionally, it assesses the metal leaching potential of concrete incorporating Conox sludges into the environment. The results show that mixture containing 10% Conox sludges as a sand substitute exhibit the highest mechanical strength but also increased porosity, water absorption, and chloride ion diffusion. The addition of mussel shells and straw fibers generally reduced mechanical properties and increased porosity in mortars, though a 20% mussel shell substitution maintained mechanical strength and chloride ion diffusion in the concrete. The combination of mussel shells with Conox sludges allowed the concrete to retain its mechanical properties, although it also increased porosity and chloride ion penetration, which may limit its use where impermeability is key. However, this increased porosity could benefit coastal erosion control structures like breakwaters and revetments, and sea walls. Moreover, metal leaching from concrete incorporating Conox sludges remained within established safety limits. Despite these challenges, the materials show promise for non-structural applications or projects where sustainability is prioritized. Our research lays the foundation and opens new possibilities for future investigations that innovate in the combination of industrial wastes, aiming to create more sustainable construction materials with a reduced impact on biodiversity
Impaired communication at the neuromotor axis during Degenerative Cervical Myelopathy
Get PDFDegenerative Cervical Myelopathy (DCM) is a progressive neurological condition characterized by structural alterations in the cervical spine, resulting in compression of the spinal cord. While clinical manifestations of DCM are well-documented, numerous unanswered questions persist at the molecular and cellular levels. In this study, we sought to investigate the neuromotor axis during DCM. We use a clinically relevant mouse model, where after 3 months of DCM induction, the sensorimotor tests revealed a significant reduction in both locomotor activity and muscle strength compared to the control group. Immunohistochemical analyses showed alterations in the gross anatomy of the cervical spinal cord segment after DCM. These changes were concomitant with the loss of motoneurons and a decrease in the number of excitatory synaptic inputs within the spinal cord. Additionally, the DCM group exhibited a reduction in the endplate surface, which correlated with diminished presynaptic axon endings in the supraspinous muscles. Furthermore, the biceps brachii (BB) muscle exhibited signs of atrophy and impaired regenerative capacity, which inversely correlated with the transversal area of remnants of muscle fibers. Additionally, metabolic assessments in BB muscle indicated an increased proportion of oxidative skeletal muscle fibers. In line with the link between neuromotor disorders and gut alterations, DCM mice displayed smaller mucin granules in the mucosa layer without damage to the epithelial barrier in the colon. Notably, a shift in the abundance of microbiota phylum profiles reveals an elevated Firmicutes-to-Bacteroidetes ratio—a consistent hallmark of dysbiosis that correlates with alterations in gut microbiota-derived metabolites. Additionally, treatment with short-chain fatty acids stimulated the differentiation of the motoneuron-like NSC34 cell line. These findings shed light on the multifaceted nature of DCM, resembling a synaptopathy that disrupts cellular communication within the neuromotor axis while concurrently exerting influence on other systems. Notably, the colon emerges as a focal point, experiencing substantial perturbations in both mucosal barrier integrity and the delicate balance of intestinal microbiota
Capital Asset Pricing Model and Ordered Weighted Average Operator for Selecting Investment Portfolios
Get PDFThe main objective of this article is to present the formulation of a Capital Asset Pricing Model ordered weighted average CAPMOWAand its extensions, called CAPM-induced OWA (CAPMIOWA), CAPM Bonferroni OWA (CAPMBon-OWA), and CAPM Bonferroni-induced OWA CAPMBon-IOWA. A step-by-step process for applying this new proposal in a real case of formulating investment portfolios is generated. These methods show several scenarios, considering the attitude, preferences, and relationship of each argument, when underestimation or overestimation of the information by the decision maker may influence the decision-making process regarding portfolio investments. Finally, the complexity of the method and the incorporation of soft information into the modeling process lead to generating a greater number of scenarios and reflect the attitudes and preferences of decision makers
Revision of the genus Digonis (Lepidoptera, Geometridae): new species and new genera
Get PDFThe taxonomic study of the Chilean Ennomini genera is still in its early stages. Within this group, the maculation patterns of Chilean species are uniform and often inadequate for distinguishing between many species, compounded by a lack of taxonomic revisions focused on the genera within the tribe. In this study, the genus Digonis Butler, 1882, is reviewed and redefined based on characteristics of wing patterns and genitalia. Digonis comprises the following five species: D. aspersa Butler, 1882, D. cervinaria (Blanchard, 1852), D. punctifera Butler, 1882, D. gungnir Ramos-González & Parra, sp. nov., and D. apocrypha Ramos-González & Parra, sp. nov. Additionally, D. cuprea Butler, 1882 is synonymized with D. cervinaria (Blanchard, 1852), and all varieties of D. punctifera Butler, 1882, and D. cuprea are synonymized with their respective species. Furthermore, two new genera are introduced: Phasmadigonis Ramos-González & Parra, gen. nov., erected for P. alba (Butler, 1882), comb. nov., and Gugnelve Ramos-González & Parra, gen. nov., established for G. butleri Ramos-González & Parra, sp. nov. With the species and genus descriptions, a comparative diagnosis, genitalia illustrations for all species, and wing venation for each genus are provided
The development of the central nervous system and human neural stem cells
No full textThe development of the nervous system is a long process that begins during early stages of embryonic growth. Morphologically, primordial structures of the nervous system begin to form during the neurulation process. This then continues with the formation of telencephalic vesicles, the brain, spinal cord, and accompanying structures. For practical reason, most of the research dealing with the developmental process of the nervous system have used experimental model organisms and thus, we have gained important insights on how the process unfold across various species. Therefore, while we will focus on human development, research using model organisms will be included to discuss more detailed mechanistic insights. In this regard, evolution dictates not only the conservation of the developmental process with common ground across vertebrates but also finding important variations. As an example, although mammals, birds, and amphibians all undergo secondary neurulation, they have differences in primary neurulation. Regardless of that, experimental models have been instrumental in providing answer to the etiology of a number of human disorders, especially in cases where human mutations have been evaluated. Importantly, in recent years human-specific mechanistic insights have been achieved with the use of induced pluripotent stem cells (IPSCs) technology
Significance of vitamin C in cancer prevention and therapy: A review
No full textThe relationship between vitamin C and cancer is still being studied and is associated with antioxidant, pro-oxidant, and gene expression regulator properties. Vitamin C is a water-soluble antioxidant associated with the prevention of the common cold and is also a cofactor of hydrolases that participate in the synthesis of collagen and catecholamines and in the regulation of gene expression. This review explores the role of vitamin C in cancer clinical trials and the aspects to consider in future studies, such as plasmatic vitamin C and metabolite excretion recording, and metabolism and transport of vitamin C into cancer cells. The reviewed studies show that vitamin C intake from natural sources can prevent the development of pulmonary and breast cancer and that vitamin C synergizes with gemcitabine and erlotinib in pancreatic cancer. Vitamin C homeostasis is controlled mainly by four regulatory processes: (i) intestinal absorption (bioavailability), (ii) accumulation and distribution in tissues, (iii) utilization and recycling, and (iv) renal excretion and reabsorption. In vitro assays reveal that vitamin C synergizes with DNA-methyl transferase inhibitors. However, vitamin C was not associated with cancer prevention in a Mendelian randomized study. The effects of vitamin C on cancer progression depend on the route of administration. It is concluded that the role of vitamin C in the prevention and treatment of cancer is still an ongoing area of research. It is necessary that new phase II and III clinical trials be performed to collect stronger evidence of the therapeutic role of vitamin C in cancer. Clinical trials with Intravenous Ascorbic Acid as a co-adjuvant in radiotherapy or chemotherapies with gemcitabine, erlotinib, and DNA Methyltransferases inhibitors are assays in development with promising results. It is expected that new studies will reveal more about the mechanisms of the anti-cancer action of vitamin C, with new, well-structured phase II and III clinical trials performed to confirm its proposed beneficial effect on cancer prevention and treatment