Emerging Roles of microRNAs in Cystic Fibrosis — From Pathogenesis to Development of New Therapies

As essential components of the regulatory system of gene expression, microRNAs (miRNAs) have been shown to influence development, severity, prognosis, and/or progression of a variety of inherited diseases. Differential expression studies have evidenced an impact of miRNAs on lung disease development in chronic obstructive pulmonary disease (COPD), asthma, lung inflammation, consequences of smoke exposure and airway allergy in human and in animal models of the diseases. Recent clinical and cell-based studies have revealed specific alterations of miRNA expression in cystic fibrosis (CF). Here we critically review the major findings concerning altered miRNA expression in CF airway epithelium, in particular with respect to CF transmembrane conductance regulator (CFTR) expression, innate immunity, and epithelial differentiation. Finally, we explore strategies to exploit these changes with the aim of innovative therapeutic benefits

From signals to music: a bottom-up approach to the structure of neuronal activity

Introduction: The search for the “neural code” has been a fundamental quest in neuroscience, concerned with the way neurons and neuronal systems process and transmit information. However, the term “code” has been mostly used as a metaphor, seldom acknowledging the formal definitions introduced by information theory, and the contributions of linguistics and semiotics not at all. The heuristic potential of the latter was suggested by structuralism, which turned the methods and findings of linguistics to other fields of knowledge. For the study of complex communication systems, such as human language and music, the necessity of an approach that considers multilayered, nested, structured organization of symbols becomes evident. We work under the hypothesis that the neural code might be as complex as these human-made codes. To test this, we propose a bottom-up approach, constructing a symbolic logic in order to translate neuronal signals into music scores. Methods: We recorded single cells’ activity from the rat’s globus pallidus pars interna under conditions of full alertness, blindfoldedness and environmental silence. We analyzed the signals with statistical, spectral, and complex methods, including Fast Fourier Transform, Hurst exponent and recurrence plot analysis. Results: The results indicated complex behavior and recurrence graphs consistent with fractality, and a Hurst exponent >0.5, evidencing temporal persistence. On the whole, these features point toward a complex behavior of the time series analyzed, also present in classical music, which upholds the hypothesis of structural similarities between music and neuronal activity. Furthermore, through our experiment we performed a comparison between music and raw neuronal activity. Our results point to the same conclusion, showing the structures of music and neuronal activity to be homologous. The scores were not only spontaneously tonal, but they exhibited structure and features normally present in human-made musical creations. Discussion: The hypothesis of a structural homology between the neural code and the code of music holds, suggesting that some of the insights introduced by linguistic and semiotic theory might be a useful methodological resource to go beyond the limits set by metaphoric notions of “code.”Fil: Noel, Gabriel David. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Instituto de Altos Estudios Sociales; ArgentinaFil: Mugno, Lionel E.. Conservatorio "Alfredo Luis Schiuma"; ArgentinaFil: Andres, Daniela Sabrina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Tecnologias Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologias Emergentes y Ciencias Aplicadas.; Argentina. Universidad Nacional de San Martin. Escuela de Ciencia y Tecnologia. Laboratorio de Neuroingenieria.; Argentin

Wood density and tree size used as cues to locate and excavate cavities in two <i>Colaptes</i> woodpeckers inhabiting a threatened southern temperate forest of Argentina

Nest-site selection is crucial for birds’ breeding success and, therefore, studies on this topic are critical in order to understand what features species need. This is particularly important in areas with conservation issues, where habitats and/or trees with the required features may be scarce. However, little information is available on the nest-site selection patterns of woodpeckers breeding in southern temperate forests, where tree logging considerably reduced forest cover and, hence, availability of trees suitable for cavity excavation. In addition, previous studies did not include assessments at different spatial scales nor including quantitative wood density data. Therefore, the main objective of this study is to assess nest-site selection patterns (at the habitat and cavity-tree scales) of the Campo Flicker Colaptes campestris and the Green-barred Woodpecker C. melanochloros breeding in a threatened southern temperate forest of central-east Argentina. Moreover, we report the first wood density data of the trees used by these two woodpeckers when excavating cavities and assess niche partitioning by comparing their cavities and cavity-trees to one another. To assess selection at a habitat scale (recording forest cover and edge of stands and trees), we compared selected breeding habitats to randomly found habitats. At a tree-scale (recording tree height, diameter, wood density and wood decay status), we compared cavity-trees to randomly found trees. Most cavities were excavated in medium (DBH = 20–35 cm) or large (&gt;35 cm) size trees with wood density &lt; 0.5 g/cm3. Generalized linear models indicated that woodpeckers’ propensity to excavate a new cavity was negatively correlated with tree wood density (which was negatively correlated to wood decay status) and positively to tree size. Both woodpecker species focused more importantly on tree features compared to habitat features when excavating cavities. Because forest patches containing mid- and large-sized trees with main stems and/or branches with wood softened by decay processes have become less abundant in these forests due to uncontrolled logging actions, we emphasize the need to conserve trees with these characteristics to ensure the availability of the preferred features of these woodpeckers.Facultad de Ciencias Naturales y Muse

Characterizing Community Health Workers on Research Teams: Results From the Centers for Population Health and Health Disparities

Objectives. To quantify the characteristics of community health workers (CHWs) involved in community intervention research and, in particular, to characterize their job titles, roles, and responsibilities; recruitment and compensation; and training and supervision

Development of Electrochemical Sensors/Biosensors to Detect Natural and Synthetic Compounds Related to Agroalimentary, Environmental and Health Systems in Argentina: A Review of the Last Decade

Electrochemical sensors and biosensors are analytical tools, which are in continuous development with the aim of generating new analytical devices which are more reliable, cheaper, faster, sensitive, selective, and robust than others. In matrices related to agroalimentary, environmental, or health systems, natural or synthetic compounds occur which fulfil specific roles; some of them (such as mycotoxins or herbicides) may possess harmful properties, and others (such as antioxidants) beneficial ones. This imposes a challenge to develop new tools and analytical methodologies for their detection and quantification. This review summarises different aspects related to the development of electrochemical sensors and biosensors carried out in Argentina in the last ten years for application in agroalimentary, environmental, and health fields. The discussion focuses on the construction and development of electroanalytical methodologies for the determination of mycotoxins, herbicides, and natural and synthetic antioxidants. Studies based on the use of different electrode materials modified with micro/nanostructures, functional groups, and biomolecules, complemented by the use of chemometric tools, are explored. Results of the latest reports from research groups in Argentina are presented. The main goals are highlighted.Fil: Granero, Adrian Marcelo. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Fernandez, Hector. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Zon, María Alicia. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Robledo, Sebastian Noel. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ingeniería. Departamento de Tecnología Química; ArgentinaFil: Pierini, Gastón Dario. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Di Tocco, Aylen. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Carrillo Palomino, Roodney Alberto. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Maccio, Sabrina Antonella. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Riberi, Walter Iván. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Arevalo, Fernando Javier. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; Argentin

Dysregulated Proinflammatory and Fibrogenic Phenotype of Fibroblasts in Cystic Fibrosis

Morbi-mortality in cystic fibrosis (CF) is mainly related to chronic lung infection and inflammation, uncontrolled tissue rearrangements and fibrosis, and yet the underlying mechanisms remain largely unknown. We evaluated inflammatory and fibrosis responses to bleomycin in F508del homozygous and wild-type mice, and phenotype of fibroblasts explanted from mouse lungs and skin. The effect of vardenafil, a cGMP-specific phosphodiesterase type 5 inhibitor, was tested in vivo and in culture. Responses of proinflammatory and fibrotic markers to bleomycin were enhanced in lungs and skin of CF mice and were prevented by treatment with vardenafil. Purified lung and skin fibroblasts from CF mice proliferated and differentiated into myofibroblasts more prominently and displayed higher sensitivity to growth factors than those recovered from wild-type littermates. Under inflammatory stimulation, mRNA and protein expression of proinflammatory mediators were higher in CF than in wild-type fibroblasts, in which CFTR expression reached similar levels to those observed in other non-epithelial cells, such as macrophages. Increased proinflammatory responses in CF fibroblasts were reduced by half with submicromolar concentrations of vardenafil. Proinflammatory and fibrogenic functions of fibroblasts are upregulated in CF and are reduced by vardenafil. This study provides compelling new support for targeting cGMP signaling pathway in CF pharmacotherapy

Genome-wide interaction of genotype by erythrocyte n-3 fatty acids contributes to phenotypic variance of diabetes-related traits

BACKGROUND: Little is known about the interplay between n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level. The present study aimed to examine variance contributions of genotype by environment (GxE) interactions for different erythrocyte n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level in a non-Hispanic white population living in the U.S.A. (n = 820). A tool for Genome-wide Complex Trait Analysis (GCTA) was used to estimate the genome-wide GxE variance contribution of four diabetes-related traits: HOMA-Insulin Resistance (HOMA-IR), fasting plasma insulin, glucose and adiponectin. A GxE genome-wide association study (GWAS) was conducted to further elucidate the GCTA results. Replication was conducted in the participants of the Boston Puerto Rican Health Study (BPRHS) without diabetes (n = 716). RESULTS: In GOLDN, docosapentaenoic acid (DPA) contributed the most significant GxE variance to the total phenotypic variance of both HOMA-IR (26.5%, P-nominal = 0.034) and fasting insulin (24.3%, P-nominal = 0.042). The ratio of arachidonic acid to eicosapentaenoic acid + docosahexaenoic acid contributed the most significant GxE variance to the total variance of fasting glucose (27.0%, P-nominal = 0.023). GxE variance of the arachidonic acid/eicosapentaenoic acid ratio showed a marginally significant contribution to the adiponectin variance (16.0%, P-nominal = 0.058). None of the GCTA results were significant after Bonferroni correction (P < 0.001). For each trait, the GxE GWAS identified a far larger number of significant single-nucleotide polymorphisms (P-interaction ≤ 10E-5) for the significant E factor (significant GxE variance contributor) than a control E factor (non-significant GxE variance contributor). In the BPRHS, DPA contributed a marginally significant GxE variance to the phenotypic variance of HOMA-IR (12.9%, P-nominal = 0.068) and fasting insulin (18.0%, P-nominal = 0.033). CONCLUSION: Erythrocyte n-3 fatty acids contributed a significant GxE variance to diabetes-related traits at the genome-wide level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-781) contains supplementary material, which is available to authorized users

National mitigation potential from natural climate solutions in the tropics.

Better land stewardship is needed to achieve the Paris Agreement's temperature goal, particularly in the tropics, where greenhouse gas emissions from the destruction of ecosystems are largest, and where the potential for additional land carbon storage is greatest. As countries enhance their nationally determined contributions (NDCs) to the Paris Agreement, confusion persists about the potential contribution of better land stewardship to meeting the Agreement's goal to hold global warming below 2°C. We assess cost-effective tropical country-level potential of natural climate solutions (NCS)-protection, improved management and restoration of ecosystems-to deliver climate mitigation linked with sustainable development goals (SDGs). We identify groups of countries with distinctive NCS portfolios, and we explore factors (governance, financial capacity) influencing the feasibility of unlocking national NCS potential. Cost-effective tropical NCS offers globally significant climate mitigation in the coming decades (6.56 Pg CO2e yr-1 at less than 100 US$ per Mg CO2e). In half of the tropical countries, cost-effective NCS could mitigate over half of national emissions. In more than a quarter of tropical countries, cost-effective NCS potential is greater than national emissions. We identify countries where, with international financing and political will, NCS can cost-effectively deliver the majority of enhanced NDCs while transforming national economies and contributing to SDGs. This article is part of the theme issue 'Climate change and ecosystems: threats, opportunities and solutions'