Olive oil supplementation prevents extracellular matrix deposition and reduces prooxidant markers and apoptosis in the offspring´s heart of diabetic rats

Maternal diabetes induces fetal programming of cardiovascular diseases. Diabetes induced-cardiac fibrosis is a process that may start in utero and may be related to the prooxidant/proinflammatory environment. The aim of this study was to investigate the effect of a maternal diet enriched in olive oil on the levels of components and regulators of the extracellular matrix, on prooxidant markers and on apoptosis rate in the heart of 21-day-old offspring of diabetic rats. Maternal diabetes was induced by neonatal administration of streptozotocin. During pregnancy, diabetic and control rats were fed with diets supplemented or not with 6% olive oil. The heart of the offspring was studied at 21 days of age. We found increased deposition of collagen IV and fibronectin in the offspring´s heart of diabetic rats, which was prevented by the maternal diets enriched in olive oil. Increases in connective tissue growth factor were also prevented by the maternal diets enriched in olive oil. Prooxidant markers as well as apoptosis, which were increased in the heart of the offspring of diabetic rats, were prevented by the maternal olive oil dietary treatment. Our findings identified powerful effects of a maternal diet enriched in olive oil on the prevention of increased extracellular matrix deposition and increased prooxidant markers in the heart of 21-day-old offspring of diabetic rats.Fil: Roberti, Sabrina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Higa, Romina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Sato, Hugo Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Gomez Ribot, Dalmiro Leonardo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Capobianco, Evangelina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

Electrodeposition of Bi thin films on n-GaAs(111)B. I. Correlation between the overpotential and the nucleation process

Bismuth thin films constitute a promising nanostructure for the fabrication of spin-based devices. To achieve this goal, it is necessary to obtain high-quality Bi layers with controlled and reproducible properties. Therefore, studies focused on the understanding of the nucleation process and the correlation between the growth conditions and the film properties are of great interest. In this work, we have studied the electrodeposition of Bi thin films onto GaAs(111)B substrates at different overpotentials. In Part I, we have analyzed the nucleation of the films by means of potentiostatic curves. The current density transients have been deconvoluted into individual processes taking into account the energy band diagram of the semiconductor electrolyte interface. The deconvolution of the current density transients indicates that Bi electrodeposition follows a 3D nucleation controlled by diffusion, accompanied by concurrent processes such as both proton adsorption and reduction. The competition of these processes is controlled by the energy distribution of the surface states at the semiconductor electrolyte interface and determines the nucleation process. The correlation between the properties of the Bi films and the Bi/GaAs interface with the nucleation process, i.e., with overpotential, is discussed in detail in Part II of this work

DataPackageR: Reproducible data preprocessing, standardization and sharing using R/Bioconductor for collaborative data analysis [version 2; referees: 2 approved, 1 approved with reservations]

A central tenet of reproducible research is that scientific results are published along with the underlying data and software code necessary to reproduce and verify the findings. A host of tools and software have been released that facilitate such work-flows and scientific journals have increasingly demanded that code and primary data be made available with publications. There has been little practical advice on implementing reproducible research work-flows for large ’omics’ or systems biology data sets used by teams of analysts working in collaboration. In such instances it is important to ensure all analysts use the same version of a data set for their analyses. Yet, instantiating relational databases and standard operating procedures can be unwieldy, with high "startup" costs and poor adherence to procedures when they deviate substantially from an analyst’s usual work-flow. Ideally a reproducible research work-flow should fit naturally into an individual’s existing work-flow, with minimal disruption. Here, we provide an overview of how we have leveraged popular open source tools, including Bioconductor, Rmarkdown, git version control, R, and specifically R’s package system combined with a new tool DataPackageR, to implement a lightweight reproducible research work-flow for preprocessing large data sets, suitable for sharing among small-to-medium sized teams of computational scientists. Our primary contribution is the DataPackageR tool, which decouples time-consuming data processing from data analysis while leaving a traceable record of how raw data is processed into analysis-ready data sets. The software ensures packaged data objects are properly documented and performs checksum verification of these along with basic package version management, and importantly, leaves a record of data processing code in the form of package vignettes. Our group has implemented this work-flow to manage, analyze and report on pre-clinical immunological trial data from multi-center, multi-assay studies for the past three years

Nitrosothiols in the immune system: Signaling and protection

Antioxidants and Redox Signaling 18.3 (2013): 288-308Significance: In the immune system, nitric oxide (NO) has been mainly associated with antibacterial defenses exerted through oxidative, nitrosative, and nitrative stress and signal transduction through cyclic GMP-dependent mechanisms. However, S-nitrosylation is emerging as a post-translational modification (PTM) involved in NO-mediated cell signaling. Recent Advances: Precise roles for S-nitrosylation in signaling pathways have been described both for innate and adaptive immunity. Denitrosylation may protect macrophages from their own S-nitrosylation, while maintaining nitrosative stress compartmentalized in the phagosomes. Nitrosothiols have also been shown to be beneficial in experimental models of autoimmune diseases, mainly through their role in modulating T-cell differentiation and function. Critical Issues: Relationship between S-nitrosylation, other thiol redox PTMs, and other NO-signaling pathways has not been always taken into account, particularly in the context of immune responses. Methods for assaying S-nitrosylation in individual proteins and proteomic approaches to study the S-nitrosoproteome are constantly being improved, which helps to move this field forward. Future Directions: Integrated studies of signaling pathways in the immune system should consider whether S-nitrosylation/denitrosylation processes are among the PTMs influencing the activity of key signaling and adaptor proteins. Studies in pathophysiological scenarios will also be of interest to put these mechanisms into broader contexts. Interventions modulating nitrosothiol levels in autoimmune disease could be investigated with a view to developing new therapiesFinanced by the Spanish Government grants CSD2007-00020 (RosasNet, Consolider-Ingenio 2010 programme), CP07/00143 (Miguel Servet programme), and PS09/00101; and PI10/0213

Mismatches between objective parameters and measured perception assessment in room acoustics: a holistic approach

Psychoacoustic research in the field of concert halls has revealed that many aspects concerning listening perception have yet to be totally understood. On the one hand, the objective room acoustics of performance spaces are reflected in parameters, some standardized and some not, but these are related to a limited number of perceptual attributes of human response. In general, these objective parameters cannot accurately describe the acoustic details due to their inherent simplification. Under these premises, impulse responses (576 receivers) are measured in 16 concert halls, according to standard procedures, and the perception and satisfaction of the occupants of the rooms are evaluated by completing a questionnaire during live concerts. Correlation analyses and multidimensional scaling (MDS) techniques have been applied to spatial and multi-band averaged values of the acoustic parameters studied (18), and the average values of users responses (1284) to the questionnaire items (26). As a first result, correlations between objective parameters and users responses show that transversality exists between them. Secondly, hierarchical clustering produces the classification of survey questions in 7 hierarchical classes. On the other hand, a lack of tuning between objective parameters and perceptual responses is observed on applying MDS analysis to the ordination of the venues from a subjective assessment and a subjectiveobjective assessment. Finally, although the results show the mismatch between objective parameters and subjective responses, a model of subjective global evaluation of the acoustics of the room from data of three orthogonal acoustic parameters is implemented, revealing a reasonably good fit.The authors wish to express their gratitude to P. Bustamante for his help, to all those who participated as listeners in this study, and to management and staff of each hall for facilitating acoustic measurements and allowing distribution of the questionnaires in their theatres. This work has been financially supported by FEDER funds and by the Ministry of Science and Technology with references Nos. BIA2003-09306, BIA2008-05485, BIA 2010-20523, and BIA 2012-36896.Giménez Pérez, A.; Cibrián Ortíz De Anda, R.; Cerdá Jordá, S.; Girón, S.; Zamarreño García, T. (2014). Mismatches between objective parameters and measured perception assessment in room acoustics: a holistic approach. Building and Environment. 74:119-131. doi:10.1016/j.buildenv.2013.12.022S1191317

Equivalence of ELISpot Assays Demonstrated between Major HIV Network Laboratories

The Comprehensive T Cell Vaccine Immune Monitoring Consortium (CTC-VIMC) was created to provide standardized immunogenicity monitoring services for HIV vaccine trials. The ex vivo interferon-gamma (IFN-γ) ELISpot is used extensively as a primary immunogenicity assay to assess T cell-based vaccine candidates in trials for infectious diseases and cancer. Two independent, GCLP-accredited central laboratories of CTC-VIMC routinely use their own standard operating procedures (SOPs) for ELISpot within two major networks of HIV vaccine trials. Studies are imperatively needed to assess the comparability of ELISpot measurements across laboratories to benefit optimal advancement of vaccine candidates.We describe an equivalence study of the two independently qualified IFN-g ELISpot SOPs. The study design, data collection and subsequent analysis were managed by independent statisticians to avoid subjectivity. The equivalence of both response rates and positivity calls to a given stimulus was assessed based on pre-specified acceptance criteria derived from a separate pilot study.Detection of positive responses was found to be equivalent between both laboratories. The 95% C.I. on the difference in response rates, for CMV (-1.5%, 1.5%) and CEF (-0.4%, 7.8%) responses, were both contained in the pre-specified equivalence margin of interval [-15%, 15%]. The lower bound of the 95% C.I. on the proportion of concordant positivity calls for CMV (97.2%) and CEF (89.5%) were both greater than the pre-specified margin of 70%. A third CTC-VIMC central laboratory already using one of the two SOPs also showed comparability when tested in a smaller sub-study.The described study procedure provides a prototypical example for the comparison of bioanalytical methods in HIV vaccine and other disease fields. This study also provides valuable and unprecedented information for future vaccine candidate evaluations on the comparison and pooling of ELISpot results generated by the CTC-VIMC central core laboratories

SPARC Endogenous Level, rather than Fibroblast-Produced SPARC or Stroma Reorganization Induced by SPARC, Is Responsible for Melanoma Cell Growth

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein whose overexpression in malignant or tumor-stromal cells is often associated with increased aggressiveness and bad prognosis in a wide range of human cancer types, particularly melanoma. We established the impact that changes in the level of SPARC produced by malignant cells and neighboring stromal cells have on melanoma growth. Melanoma cell growth in monolayer was only slightly affected by changes in SPARC levels. However, melanoma growth in spheroids was strongly inhibited upon SPARC hyperexpression and conversely enhanced when SPARC expression was downregulated. Interestingly, SPARC overexpression in neighboring fibroblasts had no effect on spheroid growth irrespective of SPARC levels expressed by the melanoma cells, themselves. Downregulation of SPARC expression in melanoma cells induced their rejection in vivo through a mechanism mediated exclusively by host polymorphonuclear cells. On the other hand, SPARC hyperexpression enhanced vascular density, collagen deposition, and fibroblast recruitment in the surrounding stroma without affecting melanoma growth. In agreement with the in vitro data, overexpression of SPARC in co-injected fibroblasts did not affect melanoma growth in vivo. All the data indicate that melanoma growth is not subject to regulation by exogenous SPARC, nor by stromal organization, but only by SPARC levels produced by the malignant cells themselves

Boletín NUESTRA AMÉRICA XXI - Desafíos y alternativas, num.65, Marzo 2022

Una excelente iniciativa del Grupo de Trabajo Crisis y economía mundial, coordinado por María Josefina Morales, Julio Gambina y Gabriela Roffinelli

A novel mechanism linking memory stem cells with innate immunity in protection against HIV-1 infection

© 2017 The Author(s). HIV infection affects 37 million people and about 1.7 million are infected annually. Among the phase III clinical trials only the RV144 vaccine trial elicited significant protection against HIV-1 acquisition, but the efficacy and immune memory were inadequate. To boost these vaccine functions we studied T stem cell memory (TSCM) and innate immunity. TSCM cells were identified by phenotypic markers of CD4+ T cells and they were further characterised into 4 subsets. These expressed the common IL-2/IL-15 receptors and another subset of APOBEC3G anti-viral restriction factors, both of which were upregulated. In contrast, CD4+ TSCM cells expressing CCR5 co-receptors and α4β7 mucosal homing integrins were decreased. A parallel increase in CD4+ T cells was recorded with IL-15 receptors, APOBEC3G and CC chemokines, the latter downmodulating CCR5 molecules. We suggest a novel mechanism of dual memory stem cells; the established sequential memory pathway, TSCM →Central →Effector memory CD4+ T cells and the innate pathway consisting of the 4 subsets of TSCM. Both pathways are likely to be activated by endogenous HSP70. The TSCM memory stem cell and innate immunity pathways have to be optimised to boost the efficacy and immune memory of protection against HIV-1 in the clinical trial