The work can be distinguished from each other by their energy expenditure and some of them could ... more The work can be distinguished from each other by their energy expenditure and some of them could benefit health according to their characteristics. Analyze and compare the characteristics of physical activity through accelerometry in working hours of women workers and administrative assistants working toilet at the University Viña del Mar. We performed a record 10 days hrs. for four days straight of energy expenditure through triaxial accelerometers to 8 auxiliary and 8 secretaries. It also makes Anthropometric and applies the IPAQ (International Physical Activity Questionnaire). According to the IPAQ, both groups are in sedentary category, but the accelerometer determines that aids walk more steps, perform more sedentary breaks and do a physical activity level higher than secretaries. There are jobs that can promote health, despite not meeting the standard considered "non sedentary", as in the case of ancillary amenities. Energy expenditure is greater in people who perfor...
Methods in molecular biology (Clifton, N.J.), 2019
High-density protein microarrays constitute a promising high-throughput platform for the characte... more High-density protein microarrays constitute a promising high-throughput platform for the characterization of protein expression patterns, biomarker discovery, and validation. Different types of protein microarrays have been described according to several features (such as content, format, and detection system) presenting advantages and disadvantages which are relevant for the specific application and purposes. Therefore, an experimental design is key for any screening based on protein microarrays assays; in fact, the data analysis strategy is directly related to the experimental design, type of protein microarray and consequently the final outcome, the data and results interpretation, is also directly linked. Here, it is proposed a systematic workflow for biomarker discovery based on tailor-made protein microarrays platforms which obtain comprehensively info for the functional protein characterization in high-throughput format.
Abstract This paper presents a crew scheduling model for rapid transit networks, where distances ... more Abstract This paper presents a crew scheduling model for rapid transit networks, where distances are not big but service frequency is very high. The crew scheduling problem has been traditionally modelled as a set covering/partitioning problem. Here, the presented approach faces the problem in a different way taking benefit from a linear payment policy and enabling an easier integration with other planning problems such as rolling stock circulations. For solving this new model, a Fix and Relax matheuristic is employed. Branch and Bound and commercial heuristics are also tested so as to compare the performance of the presented solution approach. In order to demonstrate the goodness of the results, experiments for real case studies drawn from the main Spanish train operator, RENFE, are presented showing a good balance between optimality and computational times. Compared to commercial software, computational times are reduced more than 94%, without sacrificing optimality GAP.
Platelet mitochondrial dysfunction has been identified in different diseases. Platelet mitochondr... more Platelet mitochondrial dysfunction has been identified in different diseases. Platelet mitochondrial dysfunction favors platelet activation with a considerable increase in oxidative stress, which is implicated in platelet non-responsiveness to current antiplatelet therapy. The inhibition of platelet mitochondrial dysfunction could potentially be used as a new strategy for the development of antiplatelet activity drugs. In this context, we described quinone and hydroquinone derivatives and mitochondrially targeted compounds as initial precursors for the synthesis of new antiplatelet agents.
Pneumonia, HIV/AIDS, tuberculosis, malaria and several other diseases caused by pathogens largely... more Pneumonia, HIV/AIDS, tuberculosis, malaria and several other diseases caused by pathogens largely contribute to the enormous burden of infectious diseases. Over the last few decades, the impact of infectious diseases on a population has been drastic and remains a major health concern even today. Despite advances in science and technology in this era of health and development, there is a substantial knowledge gap in our understanding of the molecular basis of these infectious diseases. The availability of valuable genomic information for a number of pathogens and their hosts has improved our understanding of disease pathogenesis but has not always been useful in addressing important biological questions. The primary reason lies in the fact that genes do not best reflect the status of a cell. Proteins represent the functional molecules of a cell and are ultimately responsible for controlling most aspects of cellular function. Their existence as different isoforms owing to posttranslat...
Methods in molecular biology (Clifton, N.J.), 2018
Phage-display technology constitutes a powerful tool for the generation of specific antibodies ag... more Phage-display technology constitutes a powerful tool for the generation of specific antibodies against a predefined antigen. The main advantages of phage-display technology in comparison to conventional hybridoma-based techniques are: (1) rapid generation time and (2) antibody selection against an unlimited number of molecules (biological or not). However, the main bottleneck with phage-display technology is the validation strategies employed to confirm the greatest number of antibody fragments. The development of new high-throughput (HT) techniques has helped overcome this great limitation. Here, we describe a new method based on an array technology that allows the deposition of hundreds to thousands of phages by micro-contact on a unique nitrocellulose surface. This setup comes in combination with bioinformatic approaches that enables simultaneous affinity screening in a HT format of antibody-displaying phages.
CIBA Revista Iberoamericana de las Ciencias Biológicas y Agropecuarias, 2014
La formación científica del estudiante de agronomía tradicionalmente ha estado arraigada en los m... more La formación científica del estudiante de agronomía tradicionalmente ha estado arraigada en los modelos conductista que vinculan su quehacer profesional al desarrollo de habilidades y destrezas tecnológicas, con claros tintes pragmáticos y utilitaristas. Bajo este contexto, las instituciones de educación superior en América Latina, y particularmente en México, no han sabido aportar abordajes modélicos que faculten el tránsito inteligente hacia mejores formas de intervención didáctica, en busca de reorientar la formación científica del estudiante, lo que eventualmente permita dotar a los maestros de los fundamentos para alfabetizar científicamente a los futuros profesionales de las ciencias agrícolas. Atendiendo esta necesidad, el presente capítulo expone los resultados obtenidos en la aplicación de una propuesta didáctica constructivista relacionada con la alfabetización científica del estudiante de ciencias agrícolas. Registrada a lo largo de 11 años, se presentan los resultados en...
Guanosine is a natural product and an endogenous nucleoside that has shown to increase during myo... more Guanosine is a natural product and an endogenous nucleoside that has shown to increase during myocardial ischemia. Platelets are critically involved in ischemic coronary events. It remains unknown, however, whether guanosine may affect platelet activation and function. We sought to investigate the potential antiplatelet and antithrombotic properties of guanosine and decipher the mechanisms behind. We firstly assessed the effects of guanosine on platelet activation/aggregation upon stimulation with several platelet agonists including adenosine diphosphate (ADP), collagen, arachidonic acid (AA), and TRAP-6. Guanosine antithrombotic potential was also evaluated both in vitro (Badimon perfusion chamber) and in vivo (murine model). In addition we assessed any potential effect on bleeding. At a mechanistic level we determined the release of thromboxane B2, intraplatelet cAMP levels, the binding affinity on platelet membrane, and the activation/phosphorylation of protein kinase A (PKA), ph...
Selected adenosine A2A receptor agonists (PSB-15826, PSB-12404, and PSB-16301) have been evaluate... more Selected adenosine A2A receptor agonists (PSB-15826, PSB-12404, and PSB-16301) have been evaluated as new antiplatelet agents. In addition, radioligand-binding studies and receptor-docking experiments were performed in order to explain their differential biological effects on a molecular level. Among the tested adenosine derivatives, PSB-15826 was the most potent compound to inhibit platelet aggregation (EC50 0.32 ± 0.05 µmol/L) and platelet P-selectin cell-surface localization (EC50 0.062 ± 0.2 µmol/L), and to increase intraplatelets cAMP levels (EC50 0.24 ± 0.01 µmol/L). The compound was more active than CGS21680 (EC50 0.97±0.07 µmol/L) and equipotent to NECA (EC50 0.31 ± 0.05 µmol/L) in platelet aggregation induced by ADP. In contrast to the results from cAMP assays, Ki values determined in radioligand-binding studies were not predictive of the A2A agonists' antiplatelet activity. Docking studies revealed the key molecular determinants of this new family of adenosine A2A rece...
Advances in experimental medicine and biology, 2017
Leptomeningeal metastases (LM) from solid tumours, lymphoma and leukaemia are characterized by mu... more Leptomeningeal metastases (LM) from solid tumours, lymphoma and leukaemia are characterized by multifocal neurological deficits with a high mortality rate. Early diagnosis and initiation of treatment are essential to kerb neurological deterioration. However, this is not always possible as 25% of cerebrospinal fluid samples produce false-negative results at first cytological examination. The identification of biomarkers that allow stratification of individuals according to risk for developing LM would be a major benefit. Proteomic-based approaches are now in increasing use for this purpose, and these are reviewed in this chapter with a focus on cerebrospinal fluid (CSF) analyses. The construction of a CSF proteome disease database would also facilitate analysis of other neurological disorders.
RICSH Revista Iberoamericana de las Ciencias Sociales y Humanísticas, 2014
Las instituciones de educación superior en América Latina enfrentan actualmente una de sus mayore... more Las instituciones de educación superior en América Latina enfrentan actualmente una de sus mayores crisis. Pensadas como instituciones sociales encargadas de formar las nuevas generaciones de ciudadanos, bajo enfoques que aseguraban la reproducción y permanencia del modelo de desarrollo (económico, ideológico y cultural), se ven hoy confrontadas en sus principios básicos, consolidados bajo las directrices surgidas de la Ilustración, y sus consecuentes, el Racionalismo, el Positivismo y la Modernidad, mismos que le permitieron mostrar su mejor cara, aquella que proveyó de rumbo y certidumbre a la sociedad, dando lugar al discurso legitimador y a los consensos que construyeron al paso del tiempo el ideario colectivo, las aspiraciones y el sentido de pertenencia que los grandes grupos sociales exigieron.
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), Jan 3, 2017
Several studies have shown an inverse relationship between selenium status and cardiovascular hea... more Several studies have shown an inverse relationship between selenium status and cardiovascular health, although epidemiologic evidence yielded by the randomized trials did not find a beneficial effect of selenium administration. The aim of this study was to analyze the association between serum selenium levels and lipid profile adjusted by age, sex and other associated factors among a general adult population in Spain. We recruited 372 hospital employee volunteers (60 men and 312 women) with a mean age of 47 (SD: 10.9), whom were given a standardized questionnaire. Serum selenium concentration was measured by electrothermal atomization atomic absorption spectrometry. Serum copper and zinc concentrations were measured using flame atomic absorption spectrometry. The mean of serum selenium was 79.5μg/L (SD: 11.7) with no sex-dependent differences. In the multivariate linear regression analysis, the associated factors with the mean levels of selenium were: age (β=0.223; CI 95%: 0.101-0.3...
B cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy considered as the most ... more B cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy considered as the most common leukemia in the Western world. The understanding of B cell differentiation is crucial for the diagnosis, prognosis, and treatment of the disease. Areas covered: In this review, B-cell ontogeny and its relation with the CLL development, in combination with the proteomic approaches which could provide a deep characterization of the disease through the characterization of the cellular signaling pathways involved in the pathological cells is described. Expert commentary: Although conventional strategies (genome sequencing, morphology assays, and immunophenotyping by flow cytometry and/or immunochemistry) have allowed the establishment of the disease stage based on different parameters, it is still necessary to utilize novel approaches (e.g., proteomics) that have the potential to simultaneously analyze thousands of molecules to improve understanding of CLL.
Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding c... more Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding concomitant opportunistic infections. Antigen binding to the T cell receptor (TCR) triggers the recruitment of the cytosolic adaptor protein Nck to a proline-rich sequence in the cytoplasmic tail of the TCR's CD3ε subunit. Through virtual screening and using combinatorial chemistry, we have generated an orally available, low-molecular weight inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC50 (median inhibitory concentration) ~1 nM. By modulating TCR signaling, the inhibitor prevented the development of psoriasis and asthma and, furthermore, exerted a long-lasting therapeutic effect in a model of autoimmune encephalomyelitis. However, it did not prevent the generation of a protective memory response against a mouse pathogen, suggesting that the compound might not exert its effects through immunosuppression. These results suggest ...
The selection process aims sequential enrichment of phage antibody display library in clones that... more The selection process aims sequential enrichment of phage antibody display library in clones that recognize the target of interest or antigen as the library undergoes successive rounds of selection. In this review, selection methods most commonly used for phage display antibody libraries have been comprehensively described.
To gain further understanding of the general medical comorbidity of binge eating disorder (BED) b... more To gain further understanding of the general medical comorbidity of binge eating disorder (BED) beyond its association with obesity. We reviewed studies of general medical comorbidity in people with BED or clinically significant binge eating behavior beyond obesity. We also reviewed studies of BED in specific medical conditions. Three broad study categories of medical comorbidity in BED were found: cross-sectional studies of medical conditions in BED; prospective studies of medical conditions in BED; and studies of BED in specific medical conditions. Cross-sectional epidemiologic data suggest that BED is associated with medical conditions related to obesity, including diabetes, hypertension, dyslipidemias, sleep problems/disorders, and pain conditions, and that BED may be related to these conditions independent of obesity and co-occurring psychiatric disorders. Prospective data suggest that BED may be associated with type 2 diabetes and metabolic syndrome. BED or binge eating behavi...
Metallomics : integrated biometal science, Aug 13, 2016
Vanadium complexes were studied during recent years and considered as a representative of a new c... more Vanadium complexes were studied during recent years and considered as a representative of a new class of non-platinum metal antitumor agents in combination with their low toxicity. However, a few challenges still remain in the discovery of new molecular targets for these novel metal-based drugs. The study of cell signaling pathways related to vanadium drugs, which is highly critical for identifying specific targets that play an important role in the antitumor activity of vanadium compounds, is scarce. This research deals with the alterations in intracellular signaling pathways promoted by an oxovanadium(iv) complex with the flavonoid chrysin [VO(chrysin)2EtOH]2 (VOChrys) in a human osteosarcoma cell line (MG-63). Herein we report for the first time the effect of [VO(chrysin)2EtOH]2 on the relative abundance of 224 proteins, which are involved in the most common intracellular pathways. Besides, full-length human recombinant (FAK and AKT1) kinases are produced using an in situ IVTT sy...
The work can be distinguished from each other by their energy expenditure and some of them could ... more The work can be distinguished from each other by their energy expenditure and some of them could benefit health according to their characteristics. Analyze and compare the characteristics of physical activity through accelerometry in working hours of women workers and administrative assistants working toilet at the University Viña del Mar. We performed a record 10 days hrs. for four days straight of energy expenditure through triaxial accelerometers to 8 auxiliary and 8 secretaries. It also makes Anthropometric and applies the IPAQ (International Physical Activity Questionnaire). According to the IPAQ, both groups are in sedentary category, but the accelerometer determines that aids walk more steps, perform more sedentary breaks and do a physical activity level higher than secretaries. There are jobs that can promote health, despite not meeting the standard considered "non sedentary", as in the case of ancillary amenities. Energy expenditure is greater in people who perfor...
Methods in molecular biology (Clifton, N.J.), 2019
High-density protein microarrays constitute a promising high-throughput platform for the characte... more High-density protein microarrays constitute a promising high-throughput platform for the characterization of protein expression patterns, biomarker discovery, and validation. Different types of protein microarrays have been described according to several features (such as content, format, and detection system) presenting advantages and disadvantages which are relevant for the specific application and purposes. Therefore, an experimental design is key for any screening based on protein microarrays assays; in fact, the data analysis strategy is directly related to the experimental design, type of protein microarray and consequently the final outcome, the data and results interpretation, is also directly linked. Here, it is proposed a systematic workflow for biomarker discovery based on tailor-made protein microarrays platforms which obtain comprehensively info for the functional protein characterization in high-throughput format.
Abstract This paper presents a crew scheduling model for rapid transit networks, where distances ... more Abstract This paper presents a crew scheduling model for rapid transit networks, where distances are not big but service frequency is very high. The crew scheduling problem has been traditionally modelled as a set covering/partitioning problem. Here, the presented approach faces the problem in a different way taking benefit from a linear payment policy and enabling an easier integration with other planning problems such as rolling stock circulations. For solving this new model, a Fix and Relax matheuristic is employed. Branch and Bound and commercial heuristics are also tested so as to compare the performance of the presented solution approach. In order to demonstrate the goodness of the results, experiments for real case studies drawn from the main Spanish train operator, RENFE, are presented showing a good balance between optimality and computational times. Compared to commercial software, computational times are reduced more than 94%, without sacrificing optimality GAP.
Platelet mitochondrial dysfunction has been identified in different diseases. Platelet mitochondr... more Platelet mitochondrial dysfunction has been identified in different diseases. Platelet mitochondrial dysfunction favors platelet activation with a considerable increase in oxidative stress, which is implicated in platelet non-responsiveness to current antiplatelet therapy. The inhibition of platelet mitochondrial dysfunction could potentially be used as a new strategy for the development of antiplatelet activity drugs. In this context, we described quinone and hydroquinone derivatives and mitochondrially targeted compounds as initial precursors for the synthesis of new antiplatelet agents.
Pneumonia, HIV/AIDS, tuberculosis, malaria and several other diseases caused by pathogens largely... more Pneumonia, HIV/AIDS, tuberculosis, malaria and several other diseases caused by pathogens largely contribute to the enormous burden of infectious diseases. Over the last few decades, the impact of infectious diseases on a population has been drastic and remains a major health concern even today. Despite advances in science and technology in this era of health and development, there is a substantial knowledge gap in our understanding of the molecular basis of these infectious diseases. The availability of valuable genomic information for a number of pathogens and their hosts has improved our understanding of disease pathogenesis but has not always been useful in addressing important biological questions. The primary reason lies in the fact that genes do not best reflect the status of a cell. Proteins represent the functional molecules of a cell and are ultimately responsible for controlling most aspects of cellular function. Their existence as different isoforms owing to posttranslat...
Methods in molecular biology (Clifton, N.J.), 2018
Phage-display technology constitutes a powerful tool for the generation of specific antibodies ag... more Phage-display technology constitutes a powerful tool for the generation of specific antibodies against a predefined antigen. The main advantages of phage-display technology in comparison to conventional hybridoma-based techniques are: (1) rapid generation time and (2) antibody selection against an unlimited number of molecules (biological or not). However, the main bottleneck with phage-display technology is the validation strategies employed to confirm the greatest number of antibody fragments. The development of new high-throughput (HT) techniques has helped overcome this great limitation. Here, we describe a new method based on an array technology that allows the deposition of hundreds to thousands of phages by micro-contact on a unique nitrocellulose surface. This setup comes in combination with bioinformatic approaches that enables simultaneous affinity screening in a HT format of antibody-displaying phages.
CIBA Revista Iberoamericana de las Ciencias Biológicas y Agropecuarias, 2014
La formación científica del estudiante de agronomía tradicionalmente ha estado arraigada en los m... more La formación científica del estudiante de agronomía tradicionalmente ha estado arraigada en los modelos conductista que vinculan su quehacer profesional al desarrollo de habilidades y destrezas tecnológicas, con claros tintes pragmáticos y utilitaristas. Bajo este contexto, las instituciones de educación superior en América Latina, y particularmente en México, no han sabido aportar abordajes modélicos que faculten el tránsito inteligente hacia mejores formas de intervención didáctica, en busca de reorientar la formación científica del estudiante, lo que eventualmente permita dotar a los maestros de los fundamentos para alfabetizar científicamente a los futuros profesionales de las ciencias agrícolas. Atendiendo esta necesidad, el presente capítulo expone los resultados obtenidos en la aplicación de una propuesta didáctica constructivista relacionada con la alfabetización científica del estudiante de ciencias agrícolas. Registrada a lo largo de 11 años, se presentan los resultados en...
Guanosine is a natural product and an endogenous nucleoside that has shown to increase during myo... more Guanosine is a natural product and an endogenous nucleoside that has shown to increase during myocardial ischemia. Platelets are critically involved in ischemic coronary events. It remains unknown, however, whether guanosine may affect platelet activation and function. We sought to investigate the potential antiplatelet and antithrombotic properties of guanosine and decipher the mechanisms behind. We firstly assessed the effects of guanosine on platelet activation/aggregation upon stimulation with several platelet agonists including adenosine diphosphate (ADP), collagen, arachidonic acid (AA), and TRAP-6. Guanosine antithrombotic potential was also evaluated both in vitro (Badimon perfusion chamber) and in vivo (murine model). In addition we assessed any potential effect on bleeding. At a mechanistic level we determined the release of thromboxane B2, intraplatelet cAMP levels, the binding affinity on platelet membrane, and the activation/phosphorylation of protein kinase A (PKA), ph...
Selected adenosine A2A receptor agonists (PSB-15826, PSB-12404, and PSB-16301) have been evaluate... more Selected adenosine A2A receptor agonists (PSB-15826, PSB-12404, and PSB-16301) have been evaluated as new antiplatelet agents. In addition, radioligand-binding studies and receptor-docking experiments were performed in order to explain their differential biological effects on a molecular level. Among the tested adenosine derivatives, PSB-15826 was the most potent compound to inhibit platelet aggregation (EC50 0.32 ± 0.05 µmol/L) and platelet P-selectin cell-surface localization (EC50 0.062 ± 0.2 µmol/L), and to increase intraplatelets cAMP levels (EC50 0.24 ± 0.01 µmol/L). The compound was more active than CGS21680 (EC50 0.97±0.07 µmol/L) and equipotent to NECA (EC50 0.31 ± 0.05 µmol/L) in platelet aggregation induced by ADP. In contrast to the results from cAMP assays, Ki values determined in radioligand-binding studies were not predictive of the A2A agonists' antiplatelet activity. Docking studies revealed the key molecular determinants of this new family of adenosine A2A rece...
Advances in experimental medicine and biology, 2017
Leptomeningeal metastases (LM) from solid tumours, lymphoma and leukaemia are characterized by mu... more Leptomeningeal metastases (LM) from solid tumours, lymphoma and leukaemia are characterized by multifocal neurological deficits with a high mortality rate. Early diagnosis and initiation of treatment are essential to kerb neurological deterioration. However, this is not always possible as 25% of cerebrospinal fluid samples produce false-negative results at first cytological examination. The identification of biomarkers that allow stratification of individuals according to risk for developing LM would be a major benefit. Proteomic-based approaches are now in increasing use for this purpose, and these are reviewed in this chapter with a focus on cerebrospinal fluid (CSF) analyses. The construction of a CSF proteome disease database would also facilitate analysis of other neurological disorders.
RICSH Revista Iberoamericana de las Ciencias Sociales y Humanísticas, 2014
Las instituciones de educación superior en América Latina enfrentan actualmente una de sus mayore... more Las instituciones de educación superior en América Latina enfrentan actualmente una de sus mayores crisis. Pensadas como instituciones sociales encargadas de formar las nuevas generaciones de ciudadanos, bajo enfoques que aseguraban la reproducción y permanencia del modelo de desarrollo (económico, ideológico y cultural), se ven hoy confrontadas en sus principios básicos, consolidados bajo las directrices surgidas de la Ilustración, y sus consecuentes, el Racionalismo, el Positivismo y la Modernidad, mismos que le permitieron mostrar su mejor cara, aquella que proveyó de rumbo y certidumbre a la sociedad, dando lugar al discurso legitimador y a los consensos que construyeron al paso del tiempo el ideario colectivo, las aspiraciones y el sentido de pertenencia que los grandes grupos sociales exigieron.
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), Jan 3, 2017
Several studies have shown an inverse relationship between selenium status and cardiovascular hea... more Several studies have shown an inverse relationship between selenium status and cardiovascular health, although epidemiologic evidence yielded by the randomized trials did not find a beneficial effect of selenium administration. The aim of this study was to analyze the association between serum selenium levels and lipid profile adjusted by age, sex and other associated factors among a general adult population in Spain. We recruited 372 hospital employee volunteers (60 men and 312 women) with a mean age of 47 (SD: 10.9), whom were given a standardized questionnaire. Serum selenium concentration was measured by electrothermal atomization atomic absorption spectrometry. Serum copper and zinc concentrations were measured using flame atomic absorption spectrometry. The mean of serum selenium was 79.5μg/L (SD: 11.7) with no sex-dependent differences. In the multivariate linear regression analysis, the associated factors with the mean levels of selenium were: age (β=0.223; CI 95%: 0.101-0.3...
B cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy considered as the most ... more B cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy considered as the most common leukemia in the Western world. The understanding of B cell differentiation is crucial for the diagnosis, prognosis, and treatment of the disease. Areas covered: In this review, B-cell ontogeny and its relation with the CLL development, in combination with the proteomic approaches which could provide a deep characterization of the disease through the characterization of the cellular signaling pathways involved in the pathological cells is described. Expert commentary: Although conventional strategies (genome sequencing, morphology assays, and immunophenotyping by flow cytometry and/or immunochemistry) have allowed the establishment of the disease stage based on different parameters, it is still necessary to utilize novel approaches (e.g., proteomics) that have the potential to simultaneously analyze thousands of molecules to improve understanding of CLL.
Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding c... more Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding concomitant opportunistic infections. Antigen binding to the T cell receptor (TCR) triggers the recruitment of the cytosolic adaptor protein Nck to a proline-rich sequence in the cytoplasmic tail of the TCR's CD3ε subunit. Through virtual screening and using combinatorial chemistry, we have generated an orally available, low-molecular weight inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC50 (median inhibitory concentration) ~1 nM. By modulating TCR signaling, the inhibitor prevented the development of psoriasis and asthma and, furthermore, exerted a long-lasting therapeutic effect in a model of autoimmune encephalomyelitis. However, it did not prevent the generation of a protective memory response against a mouse pathogen, suggesting that the compound might not exert its effects through immunosuppression. These results suggest ...
The selection process aims sequential enrichment of phage antibody display library in clones that... more The selection process aims sequential enrichment of phage antibody display library in clones that recognize the target of interest or antigen as the library undergoes successive rounds of selection. In this review, selection methods most commonly used for phage display antibody libraries have been comprehensively described.
To gain further understanding of the general medical comorbidity of binge eating disorder (BED) b... more To gain further understanding of the general medical comorbidity of binge eating disorder (BED) beyond its association with obesity. We reviewed studies of general medical comorbidity in people with BED or clinically significant binge eating behavior beyond obesity. We also reviewed studies of BED in specific medical conditions. Three broad study categories of medical comorbidity in BED were found: cross-sectional studies of medical conditions in BED; prospective studies of medical conditions in BED; and studies of BED in specific medical conditions. Cross-sectional epidemiologic data suggest that BED is associated with medical conditions related to obesity, including diabetes, hypertension, dyslipidemias, sleep problems/disorders, and pain conditions, and that BED may be related to these conditions independent of obesity and co-occurring psychiatric disorders. Prospective data suggest that BED may be associated with type 2 diabetes and metabolic syndrome. BED or binge eating behavi...
Metallomics : integrated biometal science, Aug 13, 2016
Vanadium complexes were studied during recent years and considered as a representative of a new c... more Vanadium complexes were studied during recent years and considered as a representative of a new class of non-platinum metal antitumor agents in combination with their low toxicity. However, a few challenges still remain in the discovery of new molecular targets for these novel metal-based drugs. The study of cell signaling pathways related to vanadium drugs, which is highly critical for identifying specific targets that play an important role in the antitumor activity of vanadium compounds, is scarce. This research deals with the alterations in intracellular signaling pathways promoted by an oxovanadium(iv) complex with the flavonoid chrysin [VO(chrysin)2EtOH]2 (VOChrys) in a human osteosarcoma cell line (MG-63). Herein we report for the first time the effect of [VO(chrysin)2EtOH]2 on the relative abundance of 224 proteins, which are involved in the most common intracellular pathways. Besides, full-length human recombinant (FAK and AKT1) kinases are produced using an in situ IVTT sy...
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