Matias Blaustein | Universidad de Buenos Aires (original) (raw)
Papers by Matias Blaustein
Frontiers in Medicine, Jan 10, 2024
Frontiers in Medicine, Nov 8, 2023
Frontiers in medicine, Mar 18, 2024
Recently, using bibliometric tools, we analyzed the key actors, contents, and influence of the prevailing biomedical research agenda. Our analysis led us to conclude that fostering a more inclusive research agenda, alongside adopting epistemological frameworks that consider socio-environmental fa..., 2024
Recently, using bibliometric tools, we analyzed the key actors, contents, and influence of the pr... more Recently, using bibliometric tools, we analyzed the key actors, contents, and influence of the prevailing biomedical research agenda. Our analysis led us to conclude that fostering a more inclusive research agenda, alongside adopting epistemological frameworks that consider socio-environmental factors influencing disease transmission, could enhance our readiness to prevent and treat a wider range of diseases, ultimately leading to improved health outcomes (1, 2). Predominant health research agendas, usually in line with existing financial incentives for obtaining lucrative research results, tend to focus on therapeutic and pharmacological intervention, prioritizing innovative therapies based on molecular biology and biotechnology approaches. However, commercial interests do not necessarily align with the existing public health priorities, generating a diversity of conflicts of interest (COI) (3–9). The prevalence of health and biomedical research agendas often neglects not only the less lucrative diseases but also the study of the social and environmental determinants of health and disease, even when addressing these aspects could significantly improve population health at much lower costs. Some examples of absent studies in the health research agendas are the analysis of non-medical factors influencing health outcomes (social determinants of health), the analysis of the relationship between people and their environment (environmental health), or the evaluation of the socio-environmental factors that influence the deterioration of bodies and territories (such as the One Health approach). This issue of Frontiers in Medicine explores why these approaches are often neglected and how they could help to significantly improve health outcomes at a lower cost while also reaching social groups and minorities that are often disregarded by big pharma. A total of 14 manuscripts, including original research, perspective, opinions, brief research reports, and different types of reviews, were accepted and published.
Frontiers in Medicine, 2023
Health Education (HE) is a field that, despite being widely—almost intuitively—regarded as crucia... more Health Education (HE) is a field that, despite being widely—almost intuitively—regarded as crucial, is not usually addressed in other health-related fields and health research agendas, leaving its role and implications relegated (1).
Both health communication and community participation in health share a similar taste, ubiquitously considered important but insistent and persistent as problematic. As Morgan once described it as a perpetual allure and a persistent challenge (2).
In this article, an overview of the HE field is shared, providing a brief sample of research and key ontological and epistemological stances in order to describe HE paradigms and perspectives in tension. This typology of perspectives may help to question and analyze which HE is being—implicitly or explicitly—supported by different health initiatives. Some experiences and theories from Latin America are also shared, which may not be very well known in other geographies, and these frameworks are placed in dialogue with others fostered in the Global North. All of this we hope may contribute to discussing questions such as how can health education (HE) contribute to broader health initiatives? How is HE performed in different educational contexts? Which HE do we have and which do we want?
Frontiers in Medicine, 2024
The COVID-19 pandemic produced by the newly emerged coronavirus SARS-CoV-2 changed public health ... more The COVID-19 pandemic produced by the newly emerged coronavirus SARS-CoV-2 changed public health agendas and scientific priorities (1). During most of 2020, no vaccines or therapies were available to fight the acute respiratory disease produced by this new type of coronavirus (2). This uncertain situation led scientists to increase interdisciplinary collaborations in order to contribute to the understanding of SARS-CoV-2 infection. Therefore, several new biotechnological initiatives were carried out in extraordinary time to generate tools that could help in prevention, diagnosis and therapeutics (3). The majority of them were developed in central countries and resulted in several approaches that were distributed worldwide. However, peripheral countries, like Argentina, Brazil, Cuba, and India, have also made their own developments providing resources to local production necessary to fight against this respiratory disease (4, 5).1,2 One of these initiatives was the Argentinean AntiCovid Consortium, where we partnered with nearly 30 researchers (PIs, young researchers, postdocs and PhD students) from different scientific backgrounds, combining our knowledge and expertise to carry out a multidisciplinary strategy.3 The main objective of this Consortium was to rapidly generate scalable and economically accessible biotechnological tools. In particular, we focused on the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein, which was employed for local development of in vitro diagnostic kits and later as an antigen for vaccine development. One characteristic of the consortium was to work as horizontally as possible (each one according to his/her possibilities during the pandemic), without establishing hierarchies among members beyond those given by experience and knowledge. In line with this vision, some of the biotechnological outcomes of the consortium were published in open access peer-reviewed journals, listing the authors in alphabetical order along with an equal contribution statement (6, 7), to make the developments available to the scientific community and the society in general. In this article we will comment on the positive outcomes of this initiative, some of the drawbacks we encountered, as well as open questions and perspectives on the role of science in peripheral countries.
© Autor(es); 2023. Este es un artículo en acceso abierto, distribuido bajo los términos de una li... more © Autor(es); 2023. Este es un artículo en acceso abierto, distribuido bajo los términos de una licencia Creative Commons (https://creativecommons.org/licenses/by/4.0) que permite el uso, distribución y reproducción en cualquier medio siempre que la obra original sea correctamente citada
Alzheimers & Dementia, Dec 1, 2020
BackgroundTDP‐43 is a major component of cytoplasmic inclusions observed in neurodegenerative dis... more BackgroundTDP‐43 is a major component of cytoplasmic inclusions observed in neurodegenerative diseases like frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). To further understand the role of this predominantly nuclear RNA‐binding protein in disease‐related mRNA/protein metabolism and proteostasis, we used a combined approach with cellular and animal models that overexpress a cytoplasmic form of human TDP‐43 (TDP‐43‐ΔNLS), recapitulating ALS/FTD features.MethodHEK293 cells were transfected with empty vector or hTDP‐43‐ΔNLS followed by a method for labeling de novo translation, surface sensing of translation (SUnSET), based on puromycin (PURO) incorporation. We also assessed whether cytoplasmic TDP‐43 regulates global translation in vivo using a transgenic TDP‐43‐ΔNLS mouse model. Brain cortices from control and transgenic mice were subjected to polysome profiling and western blotting. Lastly, cellular level analysis of ongoing protein synthesis was performed by applying the SUnSET method in acute thick brain slices from control and TDP‐43‐ΔNLS mice. Immunofluorescence for TDP‐43 and PURO was performed and signal intensity was measured.ResultOur in vitro approach showed that, while control cells displayed robust puromycilation, TDP‐43‐ΔNLS positive cells exhibited reduced ongoing protein synthesis when compared to control groups. In vivo results from polysome profiling revealed a shift towards light (non‐polysomal) fractions as compared to wild‐type littermates, indicating a decrease in global mRNA translation. Cellular level analysis of ongoing protein synthesis showed that slices from control mice incubated with PURO exhibited robust cytoplasmic PURO signal in layer 5 neurons from motor cortex, and normal nuclear TDP‐43 levels similar to control (‐PURO) neurons. Slices from TDP‐43‐ΔNLS mice incubated with PURO exhibited high cytoplasmic expression of TDP‐43 and a reduction in puromycilation respect to control mice. Quantification of neuronal staining intensity revealed a significant decrease in PURO incorporation in transgenic vs. control mice.Conclusion In vitro and in vivo results indicate that cytoplasmic TDP‐43 can decrease global translation and potentially cause functional/cytotoxic effects as observed in ALS/FTD. We provide in vivo evidence (by two independent and complementary methods) for a role of mislocalized TDP‐43 in the regulation of global protein synthesis, with implications for understanding the molecular changes underlying the clinic‐pathological manifestations of TDP‐43 proteinopathies.
FEBS Letters, Feb 16, 2002
Hepatocytes are the source of plasma fibronectin (FN) which lacks the alternatively spliced EDI s... more Hepatocytes are the source of plasma fibronectin (FN) which lacks the alternatively spliced EDI segment, distinctive of oncofetal FN. When hepatic or other epithelial cells are cultured on plastic, EDI inclusion is triggered. Here we report that EDI inclusion is inhibited when hepatic cells are cultured on a basement membrane-like extracellular matrix (ECM), demonstrating a new role for the ECM in the control of gene expression. The effect is duplicated by collagen IV and laminin but not by collagen I; is not observed with another alternatively spliced FN exon (EDII); and correlates with a decrease in cell proliferation, consistently with high EDI inclusion levels observed in many physiological and pathological proliferative processes.
Since the discovery of SARS-CoV-2, several antigens have been proposed to be part of COVID-19 vac... more Since the discovery of SARS-CoV-2, several antigens have been proposed to be part of COVID-19 vaccines. The receptor binding domain (RBD) of Spike protein is one of the promising candidates to develop effective vaccines since it can induce potent neutralizing antibodies. We previously reported the production of RBD in Pichia pastoris and showed it is structurally identical to the protein produced in mammalian HEK-293T cells. In this work we designed an RBD multimer construct with the purpose of increasing RBD immunogenicity. We produced multimeric particles by a transpeptidation reaction between the RBD expressed in P. pastoris and Lumazine Synthase from Brucella abortus (BLS), which is a highly immunogenic and very stable decameric protein of 170 kDa. We vaccinated mice with two doses 30 days apart, and then we measured humoral immune response. When the number of RBD copies coupled to BLS was high (6-7 RBD molecules per BLS decamer, in average), the immune response was significantl...
BackgroundPrevious research within the field of health and biomedical sciences (HBMS) reported th... more BackgroundPrevious research within the field of health and biomedical sciences (HBMS) reported that its prevailing research agenda is determined by leading academic institutions and big pharma companies, prioritizing the exploration of novel pharmacological interventions over research on the socio-environmental determinants of disease. Unlike previous studies, which have relied primarily on qualitative analyses, the aim of this investigation is to quantitatively explore if that prevailing international research agenda influences research in semi-peripheral countries and to which extent.MethodsWe used the Web of Science database and the CorText platform to proxy the HBMS research agenda of a prestigious research institution from Latin America: Argentina’s National Research Council (CONICET). We conducted a bibliometric and lexical analysis of 16,309 HBMS scientific articles whereby CONICET was among the authors’ affiliations. The content of CONICET’s agenda was depicted through co-oc...
Membranes, 2022
Proteins in eukaryotic cells reside in different cell compartments. Many studies require the spec... more Proteins in eukaryotic cells reside in different cell compartments. Many studies require the specific localization of proteins and the detection of any dynamic changes in intracellular protein distribution. There are several methods available for this purpose that rely on the fractionation of the different cell compartments. Fractionation protocols have evolved since the first use of a centrifuge to isolate organelles. In this study, we described a simple method that involves the use of a tabletop centrifuge and different detergents to obtain cell fractions enriched in cytosolic (Cyt), plasma membrane (PM), membranous organelle (MO), and nuclear (Nu) proteins and identify the proteins in each fraction. This method serves to identify transmembrane proteins such as channel subunits as well as PM-embedded or weakly associated proteins. This protocol uses a minute amount of cell material and typical equipment present in laboratories, and it takes approximately 3 h. The process was valid...
Scientific Reports, 2022
The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate t... more The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate to develop effective COVID-19 vaccines since it can induce potent neutralizing antibodies. We have previously reported the highly efficient production of RBD in Pichia pastoris, which is structurally similar to the same protein produced in mammalian HEK-293T cells. In this work we designed an RBD multimer with the purpose of increasing its immunogenicity. We produced multimeric particles by a transpeptidation reaction between RBD expressed in P. pastoris and Lumazine Synthase from Brucella abortus (BLS), which is a highly immunogenic and very stable decameric 170 kDa protein. Such particles were used to vaccinate mice with two doses 30 days apart. When the particles ratio of RBD to BLS units was high (6–7 RBD molecules per BLS decamer in average), the humoral immune response was significantly higher than that elicited by RBD alone or by RBD-BLS particles with a lower RBD to BLS ratio (1–2...
Membranes, 2022
Proteins in eukaryotic cells reside in different cell compartments. Many studies require the spec... more Proteins in eukaryotic cells reside in different cell compartments. Many studies require the specific localization of proteins and the detection of any dynamic changes in intracellular protein distribution. There are several methods available for this purpose that rely on the fractionation of the different cell compartments. Fractionation protocols have evolved since the first use of a centrifuge to isolate organelles. In this study, we described a simple method that involves the use of a tabletop centrifuge and different detergents to obtain cell fractions enriched in cytosolic (Cyt), plasma membrane (PM), membranous organelle (MO), and nuclear (Nu) proteins and identify the proteins in each fraction. This method serves to identify transmembrane proteins such as channel subunits as well as PM-embedded or weakly associated proteins. This protocol uses a minute amount of cell material and typical equipment present in laboratories, and it takes approximately 3 h. The process was validated using endogenous and exogenous proteins expressed in the HEK293T cell line that were targeted to each compartment. Using a specific stimulus as a trigger, we showed and quantified the shuttling of a protein channel (ASIC1a, acid sensing ion channel) from the MO fraction to the PM fraction and the shuttling of a kinase from a cytosolic location to a nuclear location.
Scientific Reports, 2022
The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate t... more The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate to develop effective COVID-19 vaccines since it can induce potent neutralizing antibodies. We have previously reported the highly efficient production of RBD in Pichia pastoris, which is structurally similar to the same protein produced in mammalian HEK-293T cells. In this work we designed an RBD multimer with the purpose of increasing its immunogenicity. We produced multimeric particles by a transpeptidation reaction between RBD expressed in P. pastoris and Lumazine Synthase from Brucella abortus (BLS), which is a highly immunogenic and very stable decameric 170 kDa protein. Such particles were used to vaccinate mice with two doses 30 days apart. When the particles ratio of RBD to BLS units was high (6-7 RBD molecules per BLS decamer in average), the humoral immune response was significantly higher than that elicited by RBD alone or by RBD-BLS particles with a lower RBD to BLS ratio (1-2 RBD molecules per BLS decamer). Remarkably, multimeric particles with a high number of RBD copies elicited a high titer of neutralizing IgGs. These results indicate that multimeric particles composed of RBD covalent coupled to BLS possess an advantageous architecture for antigen presentation to the immune system, and therefore enhancing RBD immunogenicity. Thus, multimeric RBD-BLS particles are promising candidates for a protein-based vaccine.
Cell Death and Disease, 2022
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for ... more The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. Of particular interest for this topic are the signaling cascades that regulate cell survival and death, two opposite cell programs whose control is hijacked by viral infections. The AKT and the Unfolded Protein Response (UPR) pathways, which maintain cell homeostasis by regulating these two programs, have been shown to be deregulated during SARS-CoVs infection as well as in the development of cancer, one of the most important comorbidities in relation to COVID-19. Recent evidence revealed two way crosstalk mechanisms between the AKT and the UPR pathways, suggesting that they might constitute a unified homeostatic control system. Here, we review the role of the AKT and UPR pathways and their interaction in relation to SARS-CoV-2 infection as well as in tumor onset and progression. Feedback regulation between AKT and UPR pathways emerges as a master control mechanism of cell decision making in terms of survival or death and therefore represents a key potential target for developing treatments for both viral infection and cancer. In particular, drug repositioning, the investigation of existing drugs for new therapeutic purposes, could significantly reduce time and costs compared to de novo drug discovery.
Frontiers in Medicine, Jan 10, 2024
Frontiers in Medicine, Nov 8, 2023
Frontiers in medicine, Mar 18, 2024
Recently, using bibliometric tools, we analyzed the key actors, contents, and influence of the prevailing biomedical research agenda. Our analysis led us to conclude that fostering a more inclusive research agenda, alongside adopting epistemological frameworks that consider socio-environmental fa..., 2024
Recently, using bibliometric tools, we analyzed the key actors, contents, and influence of the pr... more Recently, using bibliometric tools, we analyzed the key actors, contents, and influence of the prevailing biomedical research agenda. Our analysis led us to conclude that fostering a more inclusive research agenda, alongside adopting epistemological frameworks that consider socio-environmental factors influencing disease transmission, could enhance our readiness to prevent and treat a wider range of diseases, ultimately leading to improved health outcomes (1, 2). Predominant health research agendas, usually in line with existing financial incentives for obtaining lucrative research results, tend to focus on therapeutic and pharmacological intervention, prioritizing innovative therapies based on molecular biology and biotechnology approaches. However, commercial interests do not necessarily align with the existing public health priorities, generating a diversity of conflicts of interest (COI) (3–9). The prevalence of health and biomedical research agendas often neglects not only the less lucrative diseases but also the study of the social and environmental determinants of health and disease, even when addressing these aspects could significantly improve population health at much lower costs. Some examples of absent studies in the health research agendas are the analysis of non-medical factors influencing health outcomes (social determinants of health), the analysis of the relationship between people and their environment (environmental health), or the evaluation of the socio-environmental factors that influence the deterioration of bodies and territories (such as the One Health approach). This issue of Frontiers in Medicine explores why these approaches are often neglected and how they could help to significantly improve health outcomes at a lower cost while also reaching social groups and minorities that are often disregarded by big pharma. A total of 14 manuscripts, including original research, perspective, opinions, brief research reports, and different types of reviews, were accepted and published.
Frontiers in Medicine, 2023
Health Education (HE) is a field that, despite being widely—almost intuitively—regarded as crucia... more Health Education (HE) is a field that, despite being widely—almost intuitively—regarded as crucial, is not usually addressed in other health-related fields and health research agendas, leaving its role and implications relegated (1).
Both health communication and community participation in health share a similar taste, ubiquitously considered important but insistent and persistent as problematic. As Morgan once described it as a perpetual allure and a persistent challenge (2).
In this article, an overview of the HE field is shared, providing a brief sample of research and key ontological and epistemological stances in order to describe HE paradigms and perspectives in tension. This typology of perspectives may help to question and analyze which HE is being—implicitly or explicitly—supported by different health initiatives. Some experiences and theories from Latin America are also shared, which may not be very well known in other geographies, and these frameworks are placed in dialogue with others fostered in the Global North. All of this we hope may contribute to discussing questions such as how can health education (HE) contribute to broader health initiatives? How is HE performed in different educational contexts? Which HE do we have and which do we want?
Frontiers in Medicine, 2024
The COVID-19 pandemic produced by the newly emerged coronavirus SARS-CoV-2 changed public health ... more The COVID-19 pandemic produced by the newly emerged coronavirus SARS-CoV-2 changed public health agendas and scientific priorities (1). During most of 2020, no vaccines or therapies were available to fight the acute respiratory disease produced by this new type of coronavirus (2). This uncertain situation led scientists to increase interdisciplinary collaborations in order to contribute to the understanding of SARS-CoV-2 infection. Therefore, several new biotechnological initiatives were carried out in extraordinary time to generate tools that could help in prevention, diagnosis and therapeutics (3). The majority of them were developed in central countries and resulted in several approaches that were distributed worldwide. However, peripheral countries, like Argentina, Brazil, Cuba, and India, have also made their own developments providing resources to local production necessary to fight against this respiratory disease (4, 5).1,2 One of these initiatives was the Argentinean AntiCovid Consortium, where we partnered with nearly 30 researchers (PIs, young researchers, postdocs and PhD students) from different scientific backgrounds, combining our knowledge and expertise to carry out a multidisciplinary strategy.3 The main objective of this Consortium was to rapidly generate scalable and economically accessible biotechnological tools. In particular, we focused on the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein, which was employed for local development of in vitro diagnostic kits and later as an antigen for vaccine development. One characteristic of the consortium was to work as horizontally as possible (each one according to his/her possibilities during the pandemic), without establishing hierarchies among members beyond those given by experience and knowledge. In line with this vision, some of the biotechnological outcomes of the consortium were published in open access peer-reviewed journals, listing the authors in alphabetical order along with an equal contribution statement (6, 7), to make the developments available to the scientific community and the society in general. In this article we will comment on the positive outcomes of this initiative, some of the drawbacks we encountered, as well as open questions and perspectives on the role of science in peripheral countries.
© Autor(es); 2023. Este es un artículo en acceso abierto, distribuido bajo los términos de una li... more © Autor(es); 2023. Este es un artículo en acceso abierto, distribuido bajo los términos de una licencia Creative Commons (https://creativecommons.org/licenses/by/4.0) que permite el uso, distribución y reproducción en cualquier medio siempre que la obra original sea correctamente citada
Alzheimers & Dementia, Dec 1, 2020
BackgroundTDP‐43 is a major component of cytoplasmic inclusions observed in neurodegenerative dis... more BackgroundTDP‐43 is a major component of cytoplasmic inclusions observed in neurodegenerative diseases like frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). To further understand the role of this predominantly nuclear RNA‐binding protein in disease‐related mRNA/protein metabolism and proteostasis, we used a combined approach with cellular and animal models that overexpress a cytoplasmic form of human TDP‐43 (TDP‐43‐ΔNLS), recapitulating ALS/FTD features.MethodHEK293 cells were transfected with empty vector or hTDP‐43‐ΔNLS followed by a method for labeling de novo translation, surface sensing of translation (SUnSET), based on puromycin (PURO) incorporation. We also assessed whether cytoplasmic TDP‐43 regulates global translation in vivo using a transgenic TDP‐43‐ΔNLS mouse model. Brain cortices from control and transgenic mice were subjected to polysome profiling and western blotting. Lastly, cellular level analysis of ongoing protein synthesis was performed by applying the SUnSET method in acute thick brain slices from control and TDP‐43‐ΔNLS mice. Immunofluorescence for TDP‐43 and PURO was performed and signal intensity was measured.ResultOur in vitro approach showed that, while control cells displayed robust puromycilation, TDP‐43‐ΔNLS positive cells exhibited reduced ongoing protein synthesis when compared to control groups. In vivo results from polysome profiling revealed a shift towards light (non‐polysomal) fractions as compared to wild‐type littermates, indicating a decrease in global mRNA translation. Cellular level analysis of ongoing protein synthesis showed that slices from control mice incubated with PURO exhibited robust cytoplasmic PURO signal in layer 5 neurons from motor cortex, and normal nuclear TDP‐43 levels similar to control (‐PURO) neurons. Slices from TDP‐43‐ΔNLS mice incubated with PURO exhibited high cytoplasmic expression of TDP‐43 and a reduction in puromycilation respect to control mice. Quantification of neuronal staining intensity revealed a significant decrease in PURO incorporation in transgenic vs. control mice.Conclusion In vitro and in vivo results indicate that cytoplasmic TDP‐43 can decrease global translation and potentially cause functional/cytotoxic effects as observed in ALS/FTD. We provide in vivo evidence (by two independent and complementary methods) for a role of mislocalized TDP‐43 in the regulation of global protein synthesis, with implications for understanding the molecular changes underlying the clinic‐pathological manifestations of TDP‐43 proteinopathies.
FEBS Letters, Feb 16, 2002
Hepatocytes are the source of plasma fibronectin (FN) which lacks the alternatively spliced EDI s... more Hepatocytes are the source of plasma fibronectin (FN) which lacks the alternatively spliced EDI segment, distinctive of oncofetal FN. When hepatic or other epithelial cells are cultured on plastic, EDI inclusion is triggered. Here we report that EDI inclusion is inhibited when hepatic cells are cultured on a basement membrane-like extracellular matrix (ECM), demonstrating a new role for the ECM in the control of gene expression. The effect is duplicated by collagen IV and laminin but not by collagen I; is not observed with another alternatively spliced FN exon (EDII); and correlates with a decrease in cell proliferation, consistently with high EDI inclusion levels observed in many physiological and pathological proliferative processes.
Since the discovery of SARS-CoV-2, several antigens have been proposed to be part of COVID-19 vac... more Since the discovery of SARS-CoV-2, several antigens have been proposed to be part of COVID-19 vaccines. The receptor binding domain (RBD) of Spike protein is one of the promising candidates to develop effective vaccines since it can induce potent neutralizing antibodies. We previously reported the production of RBD in Pichia pastoris and showed it is structurally identical to the protein produced in mammalian HEK-293T cells. In this work we designed an RBD multimer construct with the purpose of increasing RBD immunogenicity. We produced multimeric particles by a transpeptidation reaction between the RBD expressed in P. pastoris and Lumazine Synthase from Brucella abortus (BLS), which is a highly immunogenic and very stable decameric protein of 170 kDa. We vaccinated mice with two doses 30 days apart, and then we measured humoral immune response. When the number of RBD copies coupled to BLS was high (6-7 RBD molecules per BLS decamer, in average), the immune response was significantl...
BackgroundPrevious research within the field of health and biomedical sciences (HBMS) reported th... more BackgroundPrevious research within the field of health and biomedical sciences (HBMS) reported that its prevailing research agenda is determined by leading academic institutions and big pharma companies, prioritizing the exploration of novel pharmacological interventions over research on the socio-environmental determinants of disease. Unlike previous studies, which have relied primarily on qualitative analyses, the aim of this investigation is to quantitatively explore if that prevailing international research agenda influences research in semi-peripheral countries and to which extent.MethodsWe used the Web of Science database and the CorText platform to proxy the HBMS research agenda of a prestigious research institution from Latin America: Argentina’s National Research Council (CONICET). We conducted a bibliometric and lexical analysis of 16,309 HBMS scientific articles whereby CONICET was among the authors’ affiliations. The content of CONICET’s agenda was depicted through co-oc...
Membranes, 2022
Proteins in eukaryotic cells reside in different cell compartments. Many studies require the spec... more Proteins in eukaryotic cells reside in different cell compartments. Many studies require the specific localization of proteins and the detection of any dynamic changes in intracellular protein distribution. There are several methods available for this purpose that rely on the fractionation of the different cell compartments. Fractionation protocols have evolved since the first use of a centrifuge to isolate organelles. In this study, we described a simple method that involves the use of a tabletop centrifuge and different detergents to obtain cell fractions enriched in cytosolic (Cyt), plasma membrane (PM), membranous organelle (MO), and nuclear (Nu) proteins and identify the proteins in each fraction. This method serves to identify transmembrane proteins such as channel subunits as well as PM-embedded or weakly associated proteins. This protocol uses a minute amount of cell material and typical equipment present in laboratories, and it takes approximately 3 h. The process was valid...
Scientific Reports, 2022
The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate t... more The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate to develop effective COVID-19 vaccines since it can induce potent neutralizing antibodies. We have previously reported the highly efficient production of RBD in Pichia pastoris, which is structurally similar to the same protein produced in mammalian HEK-293T cells. In this work we designed an RBD multimer with the purpose of increasing its immunogenicity. We produced multimeric particles by a transpeptidation reaction between RBD expressed in P. pastoris and Lumazine Synthase from Brucella abortus (BLS), which is a highly immunogenic and very stable decameric 170 kDa protein. Such particles were used to vaccinate mice with two doses 30 days apart. When the particles ratio of RBD to BLS units was high (6–7 RBD molecules per BLS decamer in average), the humoral immune response was significantly higher than that elicited by RBD alone or by RBD-BLS particles with a lower RBD to BLS ratio (1–2...
Membranes, 2022
Proteins in eukaryotic cells reside in different cell compartments. Many studies require the spec... more Proteins in eukaryotic cells reside in different cell compartments. Many studies require the specific localization of proteins and the detection of any dynamic changes in intracellular protein distribution. There are several methods available for this purpose that rely on the fractionation of the different cell compartments. Fractionation protocols have evolved since the first use of a centrifuge to isolate organelles. In this study, we described a simple method that involves the use of a tabletop centrifuge and different detergents to obtain cell fractions enriched in cytosolic (Cyt), plasma membrane (PM), membranous organelle (MO), and nuclear (Nu) proteins and identify the proteins in each fraction. This method serves to identify transmembrane proteins such as channel subunits as well as PM-embedded or weakly associated proteins. This protocol uses a minute amount of cell material and typical equipment present in laboratories, and it takes approximately 3 h. The process was validated using endogenous and exogenous proteins expressed in the HEK293T cell line that were targeted to each compartment. Using a specific stimulus as a trigger, we showed and quantified the shuttling of a protein channel (ASIC1a, acid sensing ion channel) from the MO fraction to the PM fraction and the shuttling of a kinase from a cytosolic location to a nuclear location.
Scientific Reports, 2022
The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate t... more The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate to develop effective COVID-19 vaccines since it can induce potent neutralizing antibodies. We have previously reported the highly efficient production of RBD in Pichia pastoris, which is structurally similar to the same protein produced in mammalian HEK-293T cells. In this work we designed an RBD multimer with the purpose of increasing its immunogenicity. We produced multimeric particles by a transpeptidation reaction between RBD expressed in P. pastoris and Lumazine Synthase from Brucella abortus (BLS), which is a highly immunogenic and very stable decameric 170 kDa protein. Such particles were used to vaccinate mice with two doses 30 days apart. When the particles ratio of RBD to BLS units was high (6-7 RBD molecules per BLS decamer in average), the humoral immune response was significantly higher than that elicited by RBD alone or by RBD-BLS particles with a lower RBD to BLS ratio (1-2 RBD molecules per BLS decamer). Remarkably, multimeric particles with a high number of RBD copies elicited a high titer of neutralizing IgGs. These results indicate that multimeric particles composed of RBD covalent coupled to BLS possess an advantageous architecture for antigen presentation to the immune system, and therefore enhancing RBD immunogenicity. Thus, multimeric RBD-BLS particles are promising candidates for a protein-based vaccine.
Cell Death and Disease, 2022
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for ... more The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. Of particular interest for this topic are the signaling cascades that regulate cell survival and death, two opposite cell programs whose control is hijacked by viral infections. The AKT and the Unfolded Protein Response (UPR) pathways, which maintain cell homeostasis by regulating these two programs, have been shown to be deregulated during SARS-CoVs infection as well as in the development of cancer, one of the most important comorbidities in relation to COVID-19. Recent evidence revealed two way crosstalk mechanisms between the AKT and the UPR pathways, suggesting that they might constitute a unified homeostatic control system. Here, we review the role of the AKT and UPR pathways and their interaction in relation to SARS-CoV-2 infection as well as in tumor onset and progression. Feedback regulation between AKT and UPR pathways emerges as a master control mechanism of cell decision making in terms of survival or death and therefore represents a key potential target for developing treatments for both viral infection and cancer. In particular, drug repositioning, the investigation of existing drugs for new therapeutic purposes, could significantly reduce time and costs compared to de novo drug discovery.
Informe Ambiental FARN 2023: El laberinto de las transiciones. Aportes para pensar una salida socioecológica en tiempos de crisis, 2023
La consolidación del actual modelo científico hegemónico por medio de un discurso dominante cient... more La consolidación del actual modelo científico hegemónico por medio de un discurso dominante científico resulta fundamental para apuntalar el extractivismo de conocimiento académico producido en un país periférico como la Argentina. Este conocimiento termina siendo fundamental para la acumulación de ganancia empresarial en general y, en particular, de aquella vinculada con el extractivismo de lo que el Estado y las corporaciones denominan “recursos” naturales. En este artículo se explicita de qué manera operan los engranajes de dicho modelo y del mencionado discurso, a la vez que se proponen algunas coordenadas para desarrollar otra agenda para un tipo de ciencia
contrahegemónica.
El laberinto de las transiciones. Aportes para pensar una salida socioecológica en tiempos de crisis, 2023
Este año, Argentina cumple cuarenta años de democracia ininterrumpida: un hecho inédito en el paí... more Este año, Argentina cumple cuarenta años de democracia ininterrumpida: un hecho inédito en el país en los últimos cien años. La temática ambiental en la Argentina —que nace y florece a la par de la democracia en el país— en muchas circunstancias se ve opacada o relegada frente a problemáticas sociales y económicas siempre resaltadas como más urgentes, pero que sin embargo están estrechamente entrelazada con ellas. Lo ambiental es inseparable de la crisis social y económica que atraviesa el país, y estamos convencidos de que es condición necesaria para que cualquier solución sea duradera, justa y con vistas a mejorar nuestra democracia y la vida de las personas.
En esta edición del Informe Ambiental FARN buscamos realizar aportes para responder a una pregunta que parece simple: ¿cómo salimos de este laberinto? Los casos y situaciones que analizan los 48 autores y autoras que escriben en la 15a. edición del IAF, dan cuenta de que la tarea no es sencilla pero que hay caminos posibles para una transformación socioecológica integral.
Ciencias y pandemia: una epistemología para los derechos humanos, 2022
Este libro, recientemente publicado por la Editorial de la Universidad de La Plata (EDULP), reúne... more Este libro, recientemente publicado por la Editorial de la Universidad de La Plata (EDULP), reúne veinte ensayos coordinados por Juan Pablo Bohoslavsky, investigador del CONICET, ex consultor de la CEPAL, la ACNUDH y el PNUD, y experto en deuda externa y derechos humanos de la ONU. El libro, además, consta de un prólogo de Jaime Breilh, director del Doctorado en Salud, Ambiente y Sociedad y del Centro de Investigación y Laboratorios en Salud Colectiva de la UASB de Ecuador; y de un Posfacio de Mirta Roses, enviada Especial del director general de la OMS sobre COVID-19 para América Latina y el Caribe, directora emérita de la Organización Panamericana de la Salud y miembro de la Academia Nacional de Ciencias de Buenos Aires.
Tesis de Licenciatura en Filosofía, UBA - Matías Blaustein Kappelmacher, 2023
En este trabajo de tesis me propongo, mediante un enfoque transdisciplinario e interseccional, re... more En este trabajo de tesis me propongo, mediante un enfoque transdisciplinario e interseccional, realizar un análisis filosófico del cancercapitalismo, entendiendo al mismo como un proceso (relación o estructura) cuyos momentos (cáncer y capitalismo) operan en diferentes escalas o planos ontológicos con autonomía relativa y con leyes propias, pero con una lógica subyacente similar que los vincula conceptualmente en tanto formas de acumulación.