2011 IEEE International Symposium on Industrial Electronics, 2011
In this work a new test platform to develop con- trol/network codesign solutions for NCS&... more In this work a new test platform to develop con- trol/network codesign solutions for NCS's is presented, based on the NS-2 network simulation suite, and focused in the transport layer. Simulation results with the test platform are presented to know network and control relationships from a network point of view, using TCP/IP shared networks. Interesting remarks have been made, and
2009 35th Annual Conference of IEEE Industrial Electronics, 2009
Network usage of public communication networks such as Internet are unpredictable. TCPFriendness ... more Network usage of public communication networks such as Internet are unpredictable. TCPFriendness or similar criteria can become mandatory in future Internet transport protocols to prevent an Internet collapse produced by UDP based multimedia, teleoperation or NCS flows. Deadband sampling reduces the control data sent to the network, for an efficient use of the communication medium and minimizes time delays. In
Mammalian ornithine decarboxylase (ODC) is a very unstable protein which is degraded in an ATP-de... more Mammalian ornithine decarboxylase (ODC) is a very unstable protein which is degraded in an ATP-dependent manner by proteasome 26S, after making contact with the regulatory protein antizyme. PEST regions are sequences described as signals for protein degradation. The C-terminal PEST region of mammalian ODC is essential for its degradation by proteasome 26S. Mammalian histidine decarboxylase (HDC) is also a short-lived protein. The full primary sequence of mammalian HDC contains PEST-regions at both the N- and C-termini. Rat ODC and different truncated and full versions of rat HDC were expressed in vitro. In vitro degradation of rat ODC and rat 1–512 HDC were compared. Like ODC, rat 1–512 HDC is degraded mainly by an ATP-dependent mechanism. However, antizyme has no effect on the degradation of 1–512 HDC. The use of the inhibitors MG-132 and lactacystine significantly inhibited the degradation of 1–512 HDC, suggesting that a ubiquitin-dependent, proteasome 26S proteolytic pathway is involved. Results obtained with the different modifications of rat HDC containing all three PEST regions (full version, 1–656 HDC), only the N-terminal PEST region (1–512 HDC), or no PEST region (69–512 HDC), indicate that the N-terminal (1–69) fragment, but not the C-terminal fragment, determines that the HDC protein is a proteasome substrate in vitro.
Tau cDNAs from each of the six human isoforms were transfected into COS- 1 cells and, in every ca... more Tau cDNAs from each of the six human isoforms were transfected into COS- 1 cells and, in every case, more than one peptide was observed. The diversity of expressed isoforms was due to different levels of tau phosphorylation. Tau phosphorylation results in a decrease of the protein electrophoretic mobility. The major contribution to this mobility shift is due to the
The interaction of highly polymerized calf-thymus DNA with 1-aminooxy-3-N-(3-aminopropyl)-aminopr... more The interaction of highly polymerized calf-thymus DNA with 1-aminooxy-3-N-(3-aminopropyl)-aminopropane (ap-apa), an aminooxy analogue of the biogenic ornithine-derived polyamine spermidine, has been investigated by vibrational spectroscopy. Infrared and Raman spectra of DNA/ap-apa solutions, at different polyamine concentrations, were registered. The infrared spectra were extended to solutions in heavy water in order to analyze the 1500–1700cm−1 region. The spectroscopical data were discussed
The effects of histamine on polyamine uptake and metabolism was studied in a mouse mast cell line... more The effects of histamine on polyamine uptake and metabolism was studied in a mouse mast cell line (C57.1), as a cell model in which both biogenic amines are important for maintaining cell function and viability. Results obtained after incubations with exogenous histamine indicated that histamine prevents polyamine accumulation by affecting polyamine uptake. A plasma membrane transport system for polyamines has been also studied in mast cells. It seems to be a Na+-dependent uptake with high affinity for both spermine and spermidine and lower affinity for putrescine and agmatine. Polyamine uptake was reduced in both cells treated with exogenous histamine and histamine-preloaded cells. However, ornithine decarboxylase activity and cell proliferation were not affected by histamine. Incubation with histamine enhanced the spermidine/spermine acetyl transferase induction caused by N1-ethyl-N11-[(cyclopropyl)methyl]-4,8-diazaundecane, suggesting that polyamine acetylation could be another mechanism by which histamine prevents polyamine accumulation in C57.1 mast cells.
The international journal of biochemistry & cell biology, 2014
Cholesterol levels in the body are maintained through the coordinated regulation of its uptake, s... more Cholesterol levels in the body are maintained through the coordinated regulation of its uptake, synthesis, distribution, storage and efflux. However, the way cholesterol is sorted within cells remains poorly defined. The discovery of the newly described StarD4 subfamily, part of the steroidogenic acute regulatory lipid transfer (START) domain family of proteins, affords an opportunity for the study of intracellular cholesterol movement, metabolism and its disorders. The three members of this intracellular subfamily of proteins (StarD4, StarD5 and StarD6) have a similar lipid binding pocket specific for sterols (cholesterol in particular), but differing regulation and localization. The ability to bind and transport cholesterol through a non-vesicular mean suggests that they play a previously unappreciated role in cholesterol homeostasis.
Abnormal levels and hyperphosphorylation of tau protein have been proposed as the underlying caus... more Abnormal levels and hyperphosphorylation of tau protein have been proposed as the underlying cause of a group of neurodegenerative disorders collectively known as 'tauopathies'. The detrimental consequence is the loss of affinity between this protein and the microtubules, increased production of fibrillary aggregates, and the accumulation of insoluble intracellular neurofibrillary tangles. A similar phenotype can be observed in various preclinical models, which have been generated to study the role of tau protein in neurodegenerative disorders. In this study, we have analyzed the brain metabolic activity in an animal model of tauopathy (tauVLW transgenic mice), which has been previously reported to mimic some of the phenotypic features of these disorders. By using a non-invasive technique, positron emission tomography (PET), a longitudinal non-clinical follow up study was carried out during most of the lifespan of these transgenic mice, from the youth to the senescence stage...
Granzyme B (GrzB) is expressed by activated T cells and mediates cellular apoptosis. GrzB also ac... more Granzyme B (GrzB) is expressed by activated T cells and mediates cellular apoptosis. GrzB also acts as an extracellular protease involved in tissue degradation. We hypothesized that GrzB production from activated memory CD4 T cells may be associated with HIV pathogenesis. We found that stimulated memory CD4 T cells (via costimulation, cytokines, and TLR ligands) concomitantly produced GrzB and HIV. Both GrzB and HIV expression were mainly restricted to CCR5-expressing memory CD4+CD45RO+ T cells, including Th1 and Th17 subsets. Activated memory CD4 T cells also mediated tissue damage, such as disruption of intestinal epithelial monolayers. In non-human primates, CD4 T cells of rhesus macaques (pathogenic SIV hosts) expressed higher GrzB compared to African green monkeys (non-pathogenic SIV hosts). These results suggest that GrzB from CCR5+ memory CD4 T cells may have a role in cellular and tissue pathologies during HIV infection.
Polyamines are essential for cell proliferation, and their levels are elevated in many human tumo... more Polyamines are essential for cell proliferation, and their levels are elevated in many human tumours. The oncogene n-myc is known to potentiate polyamine metabolism. Neuroblastoma, the most frequent extra-cranial solid tumour in children, harbours the amplification of n-myc oncogene in 25% of the cases, and it is associated with treatment failure and poor prognosis. We evaluated several metabolic features of the human neuroblastoma cell lines Kelly, IMR-32 and SK-N-SH. We further investigated the effects of glycolysis impairment in polyamine metabolism in these cell lines. A previously unknown linkage between glycolysis impairment and polyamine reduction is unveiled. We show that glycolysis inhibition is able to trigger signalling events leading to the reduction of N-Myc protein levels and a subsequent decrease of both ornithine decarboxylase expression and polyamine levels, accompanied by cell cycle blockade preceding cell death. New anti-tumour strategies could take advantage of t...
Damnacanthal, an anthraquinone present in noni plants, targets several tyrosine kinases and has a... more Damnacanthal, an anthraquinone present in noni plants, targets several tyrosine kinases and has antitumoral effects. This study aims at getting additional insight on the potential of damnacanthal as a natural antitumor compound. The direct effect of damnacanthal on c-Met was tested by in vitro activity assays. Additionally, Western blots of c-Met phosphorylation in human hepatocellular carcinoma Hep G2 cells were performed. The antitumor effects of damnacanthal were tested by using cell growth, soft agar clonogenic, migration and invasion assays. Their mechanisms were studied by Western blot, and cell cycle, apoptosis and zymographic assays. Results show that damnacanthal targets c-Met both in vitro and in cell culture. On the other hand, damnacanthal also decreases the phosphorylation levels of Akt and targets matrix metalloproteinase-2 secretion in Hep G2 cells. These molecular effects are accompanied by inhibition of the growth and clonogenic potential of Hep G2 hepatocellular ca...
Handbook of Anticancer Drugs from Marine Origin, 2014
ABSTRACT Angiogenesis plays an essential role in tumor growth, invasion, and metastasis. Inhibiti... more ABSTRACT Angiogenesis plays an essential role in tumor growth, invasion, and metastasis. Inhibition of angiogenesis has become a major challenge in the development of new anticancer agents, with a countless number of antiangiogenic strategies being tested in preclinical and clinical trials. Nowadays the clinical development of antiangiogenic therapies seems to be unstoppable, not only for cancer, but also for an increasing number of non-neoplasic angiogenesis-related diseases. Although most of the natural compounds previously described as inhibitors of angiogenesis have been isolated from plants and terrestrial microorganisms, increasing attention is being paid to the development of marine-derived antiangiogenic agents. Marine organisms produce interesting and singular pharmacological lead compounds, derived from the large diversity of marine habitats and environmental conditions. Among the many different types of marine organisms used as a source for drug discovery, sponges represent one of the most promising sources of leads in the research of new cancer drugs. There are different strategies for angiogenesis intervention, based on the modulation of any of the different steps of the angiogenic process. In this chapter, we will provide an overview of the angiogenesis inhibitors isolated from marine sponges based on the available information regarding their primary targets or mechanism of action.
2011 IEEE International Symposium on Industrial Electronics, 2011
In this work a new test platform to develop con- trol/network codesign solutions for NCS&... more In this work a new test platform to develop con- trol/network codesign solutions for NCS's is presented, based on the NS-2 network simulation suite, and focused in the transport layer. Simulation results with the test platform are presented to know network and control relationships from a network point of view, using TCP/IP shared networks. Interesting remarks have been made, and
2009 35th Annual Conference of IEEE Industrial Electronics, 2009
Network usage of public communication networks such as Internet are unpredictable. TCPFriendness ... more Network usage of public communication networks such as Internet are unpredictable. TCPFriendness or similar criteria can become mandatory in future Internet transport protocols to prevent an Internet collapse produced by UDP based multimedia, teleoperation or NCS flows. Deadband sampling reduces the control data sent to the network, for an efficient use of the communication medium and minimizes time delays. In
Mammalian ornithine decarboxylase (ODC) is a very unstable protein which is degraded in an ATP-de... more Mammalian ornithine decarboxylase (ODC) is a very unstable protein which is degraded in an ATP-dependent manner by proteasome 26S, after making contact with the regulatory protein antizyme. PEST regions are sequences described as signals for protein degradation. The C-terminal PEST region of mammalian ODC is essential for its degradation by proteasome 26S. Mammalian histidine decarboxylase (HDC) is also a short-lived protein. The full primary sequence of mammalian HDC contains PEST-regions at both the N- and C-termini. Rat ODC and different truncated and full versions of rat HDC were expressed in vitro. In vitro degradation of rat ODC and rat 1–512 HDC were compared. Like ODC, rat 1–512 HDC is degraded mainly by an ATP-dependent mechanism. However, antizyme has no effect on the degradation of 1–512 HDC. The use of the inhibitors MG-132 and lactacystine significantly inhibited the degradation of 1–512 HDC, suggesting that a ubiquitin-dependent, proteasome 26S proteolytic pathway is involved. Results obtained with the different modifications of rat HDC containing all three PEST regions (full version, 1–656 HDC), only the N-terminal PEST region (1–512 HDC), or no PEST region (69–512 HDC), indicate that the N-terminal (1–69) fragment, but not the C-terminal fragment, determines that the HDC protein is a proteasome substrate in vitro.
Tau cDNAs from each of the six human isoforms were transfected into COS- 1 cells and, in every ca... more Tau cDNAs from each of the six human isoforms were transfected into COS- 1 cells and, in every case, more than one peptide was observed. The diversity of expressed isoforms was due to different levels of tau phosphorylation. Tau phosphorylation results in a decrease of the protein electrophoretic mobility. The major contribution to this mobility shift is due to the
The interaction of highly polymerized calf-thymus DNA with 1-aminooxy-3-N-(3-aminopropyl)-aminopr... more The interaction of highly polymerized calf-thymus DNA with 1-aminooxy-3-N-(3-aminopropyl)-aminopropane (ap-apa), an aminooxy analogue of the biogenic ornithine-derived polyamine spermidine, has been investigated by vibrational spectroscopy. Infrared and Raman spectra of DNA/ap-apa solutions, at different polyamine concentrations, were registered. The infrared spectra were extended to solutions in heavy water in order to analyze the 1500–1700cm−1 region. The spectroscopical data were discussed
The effects of histamine on polyamine uptake and metabolism was studied in a mouse mast cell line... more The effects of histamine on polyamine uptake and metabolism was studied in a mouse mast cell line (C57.1), as a cell model in which both biogenic amines are important for maintaining cell function and viability. Results obtained after incubations with exogenous histamine indicated that histamine prevents polyamine accumulation by affecting polyamine uptake. A plasma membrane transport system for polyamines has been also studied in mast cells. It seems to be a Na+-dependent uptake with high affinity for both spermine and spermidine and lower affinity for putrescine and agmatine. Polyamine uptake was reduced in both cells treated with exogenous histamine and histamine-preloaded cells. However, ornithine decarboxylase activity and cell proliferation were not affected by histamine. Incubation with histamine enhanced the spermidine/spermine acetyl transferase induction caused by N1-ethyl-N11-[(cyclopropyl)methyl]-4,8-diazaundecane, suggesting that polyamine acetylation could be another mechanism by which histamine prevents polyamine accumulation in C57.1 mast cells.
The international journal of biochemistry & cell biology, 2014
Cholesterol levels in the body are maintained through the coordinated regulation of its uptake, s... more Cholesterol levels in the body are maintained through the coordinated regulation of its uptake, synthesis, distribution, storage and efflux. However, the way cholesterol is sorted within cells remains poorly defined. The discovery of the newly described StarD4 subfamily, part of the steroidogenic acute regulatory lipid transfer (START) domain family of proteins, affords an opportunity for the study of intracellular cholesterol movement, metabolism and its disorders. The three members of this intracellular subfamily of proteins (StarD4, StarD5 and StarD6) have a similar lipid binding pocket specific for sterols (cholesterol in particular), but differing regulation and localization. The ability to bind and transport cholesterol through a non-vesicular mean suggests that they play a previously unappreciated role in cholesterol homeostasis.
Abnormal levels and hyperphosphorylation of tau protein have been proposed as the underlying caus... more Abnormal levels and hyperphosphorylation of tau protein have been proposed as the underlying cause of a group of neurodegenerative disorders collectively known as 'tauopathies'. The detrimental consequence is the loss of affinity between this protein and the microtubules, increased production of fibrillary aggregates, and the accumulation of insoluble intracellular neurofibrillary tangles. A similar phenotype can be observed in various preclinical models, which have been generated to study the role of tau protein in neurodegenerative disorders. In this study, we have analyzed the brain metabolic activity in an animal model of tauopathy (tauVLW transgenic mice), which has been previously reported to mimic some of the phenotypic features of these disorders. By using a non-invasive technique, positron emission tomography (PET), a longitudinal non-clinical follow up study was carried out during most of the lifespan of these transgenic mice, from the youth to the senescence stage...
Granzyme B (GrzB) is expressed by activated T cells and mediates cellular apoptosis. GrzB also ac... more Granzyme B (GrzB) is expressed by activated T cells and mediates cellular apoptosis. GrzB also acts as an extracellular protease involved in tissue degradation. We hypothesized that GrzB production from activated memory CD4 T cells may be associated with HIV pathogenesis. We found that stimulated memory CD4 T cells (via costimulation, cytokines, and TLR ligands) concomitantly produced GrzB and HIV. Both GrzB and HIV expression were mainly restricted to CCR5-expressing memory CD4+CD45RO+ T cells, including Th1 and Th17 subsets. Activated memory CD4 T cells also mediated tissue damage, such as disruption of intestinal epithelial monolayers. In non-human primates, CD4 T cells of rhesus macaques (pathogenic SIV hosts) expressed higher GrzB compared to African green monkeys (non-pathogenic SIV hosts). These results suggest that GrzB from CCR5+ memory CD4 T cells may have a role in cellular and tissue pathologies during HIV infection.
Polyamines are essential for cell proliferation, and their levels are elevated in many human tumo... more Polyamines are essential for cell proliferation, and their levels are elevated in many human tumours. The oncogene n-myc is known to potentiate polyamine metabolism. Neuroblastoma, the most frequent extra-cranial solid tumour in children, harbours the amplification of n-myc oncogene in 25% of the cases, and it is associated with treatment failure and poor prognosis. We evaluated several metabolic features of the human neuroblastoma cell lines Kelly, IMR-32 and SK-N-SH. We further investigated the effects of glycolysis impairment in polyamine metabolism in these cell lines. A previously unknown linkage between glycolysis impairment and polyamine reduction is unveiled. We show that glycolysis inhibition is able to trigger signalling events leading to the reduction of N-Myc protein levels and a subsequent decrease of both ornithine decarboxylase expression and polyamine levels, accompanied by cell cycle blockade preceding cell death. New anti-tumour strategies could take advantage of t...
Damnacanthal, an anthraquinone present in noni plants, targets several tyrosine kinases and has a... more Damnacanthal, an anthraquinone present in noni plants, targets several tyrosine kinases and has antitumoral effects. This study aims at getting additional insight on the potential of damnacanthal as a natural antitumor compound. The direct effect of damnacanthal on c-Met was tested by in vitro activity assays. Additionally, Western blots of c-Met phosphorylation in human hepatocellular carcinoma Hep G2 cells were performed. The antitumor effects of damnacanthal were tested by using cell growth, soft agar clonogenic, migration and invasion assays. Their mechanisms were studied by Western blot, and cell cycle, apoptosis and zymographic assays. Results show that damnacanthal targets c-Met both in vitro and in cell culture. On the other hand, damnacanthal also decreases the phosphorylation levels of Akt and targets matrix metalloproteinase-2 secretion in Hep G2 cells. These molecular effects are accompanied by inhibition of the growth and clonogenic potential of Hep G2 hepatocellular ca...
Handbook of Anticancer Drugs from Marine Origin, 2014
ABSTRACT Angiogenesis plays an essential role in tumor growth, invasion, and metastasis. Inhibiti... more ABSTRACT Angiogenesis plays an essential role in tumor growth, invasion, and metastasis. Inhibition of angiogenesis has become a major challenge in the development of new anticancer agents, with a countless number of antiangiogenic strategies being tested in preclinical and clinical trials. Nowadays the clinical development of antiangiogenic therapies seems to be unstoppable, not only for cancer, but also for an increasing number of non-neoplasic angiogenesis-related diseases. Although most of the natural compounds previously described as inhibitors of angiogenesis have been isolated from plants and terrestrial microorganisms, increasing attention is being paid to the development of marine-derived antiangiogenic agents. Marine organisms produce interesting and singular pharmacological lead compounds, derived from the large diversity of marine habitats and environmental conditions. Among the many different types of marine organisms used as a source for drug discovery, sponges represent one of the most promising sources of leads in the research of new cancer drugs. There are different strategies for angiogenesis intervention, based on the modulation of any of the different steps of the angiogenic process. In this chapter, we will provide an overview of the angiogenesis inhibitors isolated from marine sponges based on the available information regarding their primary targets or mechanism of action.
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Papers by Miguel Medina