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Productivity of the Science and Technology (S&T) sector of Latin American countries would require more public and private investment to increase. Despite significant progress in the first 15 years of this century, South American... more
Productivity of the Science and Technology (S&T) sector of Latin American countries would require more public and private investment to increase. Despite significant progress in the first 15 years of this century, South American investment in Science as percentage of GDP has been 10-fold lower than that of Europe. Though the need to increase S&T investment is clear, less obvious is whether money should go to infrastructure or human capital. Using global databases we assessed scientific productivity, number of researchers and resources devoted to S&T. We evaluated production for Europe, the Americas and China. We then focused on three Mercosur countries: Argentina, Brazil and Uruguay. Scientific production was related to S&T expenditure and to the number of researchers. We found that countries investing ~2% of their GDP may have a 5-fold variation in their productivity. Our results suggest than human capital explains a higher proportion of the S&T productivity than the total amount o...
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Clinical and molecular heterogeneity are hallmarks of chronic lymphocytic leukemia (CLL), a neoplasm characterized by accumulation of mature and clonal long-lived CD5 + B-lymphocytes. Mutational status of the IgHV gene of leukemic clones... more
Clinical and molecular heterogeneity are hallmarks of chronic lymphocytic leukemia (CLL), a neoplasm characterized by accumulation of mature and clonal long-lived CD5 + B-lymphocytes. Mutational status of the IgHV gene of leukemic clones is a powerful prognostic tool in CLL, and it is well established that unmutated CLLs (U-CLLs) have worse evolution than mutated cases. Nevertheless, progression and treatment requirement of patients can evolve independently from the mutational status. Microenvironment signaling or epigenetic changes partially explain this different behavior. Thus, we think that detailed characterization of the miRNAs landscape from patients with different clinical evolution could facilitate the understanding of this heterogeneity. Since miRNAs are key players in leukemia pathogenesis and evolution, we aim to better characterize different CLL behaviors by comparing the miRNome of clinically progressive U-CLLs vs. stable U-CLLs. Our data show up-regulation of miR-26b-...
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Recombinant protein expression has become an invaluable tool in basic and applied research. The accumulated knowledge in this field allowed the expression of thousands of protein targets in a soluble, pure, and homogeneous state,... more
Recombinant protein expression has become an invaluable tool in basic and applied research. The accumulated knowledge in this field allowed the expression of thousands of protein targets in a soluble, pure, and homogeneous state, essential for biochemical and structural analyses. A lot of progress has been achieved in the last decades, where challenging proteins were expressed in a soluble manner after evaluating different parameters such as host, strain, and fusion partner or promoter strength, among others. In this regard, we have previously developed a vector suite that allows the evaluation of different promoters and solubility enhancer-proteins, through an easy and efficient cloning strategy. Nonetheless, the proper expression of many targets remains elusive, requiring, for example, the addition of complex post-translation modifications and/or passage through specialized compartments. In order to overcome the limitations found when working with a single subcellular localization...
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Lipoprotein lipase (LPL) mRNA expression in chronic lymphocytic leukaemia (CLL) is associated with an unmutated immunoglobulin profile and poor clinical outcome. We evaluated the subcellular localization of LPL protein in CLL cells that... more
Lipoprotein lipase (LPL) mRNA expression in chronic lymphocytic leukaemia (CLL) is associated with an unmutated immunoglobulin profile and poor clinical outcome. We evaluated the subcellular localization of LPL protein in CLL cells that did or did not express LPL mRNA. Our results show that LPL protein is differently located in CLL cells depending on whether it is incorporated from the extracellular medium in mutated CLL or generated de novo by leukaemic cells of unmutated patients. The specific quantification of endogenous LPL protein correlates with mRNA expression levels and mutational IGHV status, suggesting LPL protein as a possible reliable prognostic marker in CLL.
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Lipoprotein lipase (LPL) is a central enzyme in lipid metabolism. Due to its catalytic activity, LPL is involved in metabolic pathways exploited by various solid and hematologic malignancies to provide an extra energy source to the tumor... more
Lipoprotein lipase (LPL) is a central enzyme in lipid metabolism. Due to its catalytic activity, LPL is involved in metabolic pathways exploited by various solid and hematologic malignancies to provide an extra energy source to the tumor cell. We and others described a link between the expression of LPL in the tumor cell and a poor clinical outcome of patients suffering Chronic Lymphocytic Leukemia (CLL). This leukemia is characterized by a slow accumulation of mainly quiescent clonal CD5 positive B cells that infiltrates secondary lymphoid organs, bone marrow and peripheral blood. Despite LPL being found to be a reliable molecular marker for CLL prognosis, its functional role and the molecular mechanisms regulating its expression are still matter of debate. Herein we address some of these questions reviewing the current state of the art of LPL research in CLL and providing some insights into where currently unexplored questions may lead to.
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Research Interests: Embryology, Biology, Medicine, DNA, Animals, and 4 moreCell nucleus, Zebrafish, fluorescent dyes, and Chick embryo
Chronic lymphocytic leukemia (CLL) is characterized by accumulation of clonal B cells arrested in G0/G1 stages that coexist, in different proportions, with proliferative B cells. Understanding the crosstalk between the proliferative... more
Chronic lymphocytic leukemia (CLL) is characterized by accumulation of clonal B cells arrested in G0/G1 stages that coexist, in different proportions, with proliferative B cells. Understanding the crosstalk between the proliferative subsets and their milieu could provide clues on CLL biology. We previously identified one of these subpopulations in the peripheral blood from unmutated patients that appears to be a hallmark of a progressive disease. Aiming to characterize the molecular mechanism underlying this proliferative behavior, we performed gene expression analysis comparing the global mRNA and microRNA expression of this leukemic subpopulation, and compared it with their quiescent counterparts. Our results suggest that proliferation of this fraction depend on microRNA-22 overexpression that induces phosphatase and tensin homolog downregulation and phosphoinositide 3-kinase (PI3K)/AKT pathway activation. Transfection experiments demonstrated that miR-22 overexpression in CLL B cells switches on PI3K/AKT, leading to downregulation of p27(-Kip1) and overexpression of Survivin and Ki-67 proteins. We also demonstrated that this pathway could be triggered by microenvironment signals like CD40 ligand/interleukin-4 and, more importantly, that this regulatory loop is also present in lymph nodes from progressive unmutated patients. Altogether, these results underline the key role of PI3K/AKT pathway in the generation of the CLL proliferative pool and provide additional rationale for the usage of PI3K inhibitors.
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Key Points Plasma-derived exosomes from patients with CLL exhibit different protein cargo compositions depending on disease status and progression. S100-A9 protein is overexpressed and S100-A9 cargo in exosomes activates NF-κB pathway in... more
Key Points Plasma-derived exosomes from patients with CLL exhibit different protein cargo compositions depending on disease status and progression. S100-A9 protein is overexpressed and S100-A9 cargo in exosomes activates NF-κB pathway in patients with CLL during disease progression.
Research Interests: Cancer, Biology, Inflammation, Leukemia, Cancer Biology, and 13 moreCancer Research, Medicine, Humans, Chronic Lymphocytic Leukemia, Blood, NF-kappa B, Exosomes, Clinical Sciences, Disease Progression, Proteome, Microvesicles, Cardiovascular medicine and haematology, and Paediatrics and reproductive medicine
Bovine leukemia virus (BLV) is an oncogenic deltaretrovirus that infects cattle worldwide. In Uruguay, it is estimated that more than 70% of dairy cattle are infected, causing serious economic losses due to decreased milk production,... more
Bovine leukemia virus (BLV) is an oncogenic deltaretrovirus that infects cattle worldwide. In Uruguay, it is estimated that more than 70% of dairy cattle are infected, causing serious economic losses due to decreased milk production, increased calving interval, and livestock losses due to lymphosarcoma. Several attempts to develop vaccine candidates that activate protective immune responses against BLV were performed, but up to date, there is no vaccine that ensures efficient protection and/or decreased viral transmission. The development and application of new vaccines that effectively control BLV infection represent a major challenge for countries with a high prevalence of infection. In this study, we generated two Drosophila melanogaster S2 stable cell lines capable of producing BLV virus-like particles (BLV-VLPs). One of them, BLV-VLP1, expressed both Gag and Env wild-type (Envwt) full-length proteins, whereas BLV-VLP2 contain Gag together with a mutant form of Env non-susceptib...
ABSTRACTEnvironmental factors such as the availability of oxygen are instructive cues to regulate stem cell maintenance and differentiation. We used a genetically encoded biosensor to monitor the hypoxic state of neural cells in the... more
ABSTRACTEnvironmental factors such as the availability of oxygen are instructive cues to regulate stem cell maintenance and differentiation. We used a genetically encoded biosensor to monitor the hypoxic state of neural cells in the larval brain of Drosophila. The biosensor reveals brain compartment and cell type specific levels of hypoxia. The values correlate with differential tracheolation that is observed throughout development between the central brain and the optic lobe. Neural stem cells in both compartments show the strongest hypoxia response while intermediate progenitors, neurons and glial cells reveal weaker responses. We demonstrate that the distance between a cell and the next closest tracheole is a good predictor of the hypoxic state for that cell. Our model concludes that oxygen availability is the major factor controlling the hypoxia response in the developing Drosophila brain but cell intrinsic and cell-type specific factors contribute to modulate the response in an...
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The Pho4 transcription factor is required for growth under low environmental phosphate concentrations in Saccharomyces cerevisiae. A characterization of Candida albicans pho4 mutants revealed that these cells are more susceptible to both... more
The Pho4 transcription factor is required for growth under low environmental phosphate concentrations in Saccharomyces cerevisiae. A characterization of Candida albicans pho4 mutants revealed that these cells are more susceptible to both osmotic and oxidative stress and that this effect is diminished in the presence of 5% CO2 or anaerobiosis, reflecting the relevance of oxygen metabolism in the Pho4-mediated response. A pho4 mutant was as virulent as wild type strain when assayed in the Galleria mellonella infection model and was even more resistant to murine macrophages in ex vivo killing assays. The lack of Pho4 neither impairs the ability to colonize the murine gut nor alters the localization in the gastrointestinal tract. However, we found that Pho4 influenced the colonization of C. albicans in the mouse gut in competition assays; pho4 mutants were unable to attain high colonization levels when inoculated simultaneously with an isogenic wild type strain. Moreover, pho4 mutants d...
Invasive candidiasis often arises from translocation of endogenous yeasts from the gastrointestinal tract to the bloodstream. Here we describe that both wild type and TLR2-/- mice strains, orally administered with Candida albicans yeasts,... more
Invasive candidiasis often arises from translocation of endogenous yeasts from the gastrointestinal tract to the bloodstream. Here we describe that both wild type and TLR2-/- mice strains, orally administered with Candida albicans yeasts, display similar sustained high level of gut colonization when oral antibacterial treatment is present, while removal of antibiotic treatment causes a progressive clearance of yeasts in control but not in TLR2-/- mice. Fungal invasion of internal organs, following immunosuppression of colonized mice, was increased in TLR2-/- mice. These results point out to a role of TLR2 in gut protection against colonization and endogenous invasion by C. albicans.
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From October 1993 to May 1994, we performed 35 total hip arthroplasties (20 women) using a Charnley type modular 28 head manufactured by Medical Tee Brazil. 9 fractures through the neck of the stem prostheses occurred, all but 1 in men,... more
From October 1993 to May 1994, we performed 35 total hip arthroplasties (20 women) using a Charnley type modular 28 head manufactured by Medical Tee Brazil. 9 fractures through the neck of the stem prostheses occurred, all but 1 in men, after mean 4 (0.3-6) years. All fractures were due to an inadequate confluent radius causing abnormal transmission forces through the neck. The higher the load (men, heavy body weight), the greater the risk of fracture. The metallographic, chemical and microhardness analyses showed no abnormalities. We ascribe these fractures to faulty design of the stem prosthesis.
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Resumen: La realización de una cartografía geológica de calidad en el área de Viana do BoloA Gudiña ha permitido establecer la sucesión estratigráfica del Paleozoico inferior y la estructura del Antiforme del Ollo de Sapo en este sector.... more
Resumen: La realización de una cartografía geológica de calidad en el área de Viana do BoloA Gudiña ha permitido establecer la sucesión estratigráfica del Paleozoico inferior y la estructura del Antiforme del Ollo de Sapo en este sector. La sucesión estratigráfica está ...
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The objective of this article is to describe and understand coping strategies for facing a crisis caused by unemployment in families with adolescent children in the city of Bogota. The conceptual framework for the study is the systemic... more
The objective of this article is to describe and understand coping strategies for facing a crisis caused by unemployment in families with adolescent children in the city of Bogota. The conceptual framework for the study is the systemic approach that facilitates a relational ...
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Candida albicans is a common resident of the oral cavity, gastrointestinal tract and vagina in healthy humans where it establishes a commensal relationship with the host. Colonization of the gut, which is an important niche for the... more
Candida albicans is a common resident of the oral cavity, gastrointestinal tract and vagina in healthy humans where it establishes a commensal relationship with the host. Colonization of the gut, which is an important niche for the microbe, may lead to systemic dissemination and disease upon alteration of host defences. Understanding the mechanisms responsible for the adaptation of C. albicans to the gut is therefore important for the design of new ways of combating fungal diseases. In this review we discuss the available models to study commensalism of this yeast, the main mechanisms controlling the establishment of the fungus, such as microbiota, mucus layer and antimicrobial peptides, and the gene regulatory circuits that ensure its survival in this niche.
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To investigate whether Cek2 (as Cek1) is involved in the biogenesis of the fungal cell wall and to uncover differences and similitudes between both proteins. We used molecular genetics to characterize the role of Cek2 in MTL-heterozygous... more
To investigate whether Cek2 (as Cek1) is involved in the biogenesis of the fungal cell wall and to uncover differences and similitudes between both proteins. We used molecular genetics to characterize the role of Cek2 in MTL-heterozygous cells. Deletion of CEK2 (similar to CEK1) renders cells sensitive to cell wall interfering drugs and, when overexpressed, Cek2 can become phosphorylated upon the same stimuli that activate Cek1. This is dependent on elements of the sterile-vegetative growth (SVG) pathway. Cek2, contrary to Cek1, mediates a transcriptional activity in a C. albicans-adapted two-hybrid system that is essential for Cek1-Cek2 interaction. Cek2 has a cryptic role in cell wall biogenesis and its role is not entirely redundant to Cek1.
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ABSTRACT
Abstract. Dietary protein and/or calorie insufficiencies represent an important problem in elderly patients. The biological and clinical implications, and particu- larly the influence on bone mass of undernutrition in the elderly, have... more
Abstract. Dietary protein and/or calorie insufficiencies represent an important problem in elderly patients. The biological and clinical implications, and particu- larly the influence on bone mass of undernutrition in the elderly, have not been completely defined, although several ...
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ABSTRACT
Candida albicans is a member of the human microbiota, colonizing both the vaginal and gastrointestinal tracts. This yeast is devoid of a life style outside the human body and the mechanisms underlying the adaptation to the commensal... more
Candida albicans is a member of the human microbiota, colonizing both the vaginal and gastrointestinal tracts. This yeast is devoid of a life style outside the human body and the mechanisms underlying the adaptation to the commensal status remain to be determined. Using a model of mouse gastrointestinal colonization, we show here that C. albicans stably colonizes the mouse gut in about 3 days starting from a dose as low as 100 cells, reaching steady levels of around 10(7) cells/g of stools. Using fluorescently labeled strains, we have assessed the competition between isogenic populations from different sources in cohoused animals. We show that long term (15 days) colonizing cells have increased fitness in the gut niche over those grown in vitro or residing in the gut for 1-3 days. Therefore, two distinct states, proliferation and adaptation, seem to exist in the adaptation of this fungus to the mouse gut, a result with potential significance in the prophylaxis and treatment of Candida infections.
The SWAT model has been recently validated for streamflow at Quequen Grande river watershed (935.533 has), as a part of an international bigger project focused on the evaluation of changes in water productivity against potential future... more
The SWAT model has been recently validated for streamflow at Quequen Grande river watershed (935.533 has), as a part of an international bigger project focused on the evaluation of changes in water productivity against potential future scenarios of climate change. SWAT was chosen as watershed scale model since it constitutes a valuable tool to study the impact of potential climate and land use changes, as well as the impact of management practices and fertilizer and pesticide use on water sources, in agricultural watersheds. SWAT was calibrated for the period 1996-2000 and validated for 2001-2006. Model predictions for daily and monthly streamflow presented Nash Sutcliffe coefficients of 0,37 and 0,61 respectively, for the validation period. Daily predictions for this watershed were acceptable, since there was not a representative network of rain gages to cover the almost one million hectares of the watershed. The model also succeeds on predicting a significant change on average str...