http://sedici.unlp.edu.ar:80/handle/10915/125300 Fri, 13 Nov 2026 03:31:26 GMT 2026-11-13T03:31:26Z http://sedici.unlp.edu.ar:80/handle/10915/125649 Revision Physiological Mini Reviews; vol. 10, no. 1 Primary cilia are microtubule based organelles that sense and transduce multiple extracellular signals to the interior of the cell through several signaling pathways. Ciliary defects lead to different pathologies. Interestingly, decreased ciliary expression has been associated with different types of cancer. In this review, we discuss the function and dynamics of primary cilia, their relation to different diseases and in particular their role in cancer, and how they can be explored as potential therapeutic targets. Wed, 01 Feb 2017 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/125649 2017-02-01T00:00:00Z Primary cilia are microtubule based organelles that sense and transduce multiple extracellular signals to the interior of the cell through several signaling pathways. Ciliary defects lead to different pathologies. Interestingly, decreased ciliary expression has been associated with different types of cancer. In this review, we discuss the function and dynamics of primary cilia, their relation to different diseases and in particular their role in cancer, and how they can be explored as potential therapeutic targets. http://sedici.unlp.edu.ar:80/handle/10915/125648 Revision Physiological Mini Reviews; vol. 10, no. 6 The role of splicing factors in pathological processes is increasingly documented. This is particularly evident in the pathologies affecting the nervous system where either the mis-folding or aggregation of RNA binding proteins is a key event in triggering the neurodegeneration. The aggregation of TDP-43 is the major distinguishing feature of most cases of Amyotrophic Lateral Sclerosis (ALS). There is still a significant uncertainty in regards to many aspects concerning the nature of the aggregates and their functional consequences. The biochemical and genetic aspects of TDP-43 aggregation need further definition, as new therapies could be directed towards them. A better understanding of TDP-43 structure and interactions is needed, from what we currently know it has been possible to construct cellular and animal models of TDP- 43 ALS like aggregation. Using these models drugs that can revert aggregation and recover function have been identified. Finally, ALS is a disease that occurs mostly during the fifth to the seventh decade of life. In this respect, it has been observed that the onset of the locomotion defect in an ALS fly model coincides with an age-related 4-fold drop in TBPH levels (the Drosophila TDP43 orthologous), similar TDP 43 reduction with age was observed in mice brain. Thus, understanding the relationship between aging and TDP-43 production and mis-folding in cell culture, animal models, and human tissues might provide further clues to explain the time of disease onset. Fri, 01 Dec 2017 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/125648 2017-12-01T00:00:00Z The role of splicing factors in pathological processes is increasingly documented. This is particularly evident in the pathologies affecting the nervous system where either the mis-folding or aggregation of RNA binding proteins is a key event in triggering the neurodegeneration. The aggregation of TDP-43 is the major distinguishing feature of most cases of Amyotrophic Lateral Sclerosis (ALS). There is still a significant uncertainty in regards to many aspects concerning the nature of the aggregates and their functional consequences. The biochemical and genetic aspects of TDP-43 aggregation need further definition, as new therapies could be directed towards them. A better understanding of TDP-43 structure and interactions is needed, from what we currently know it has been possible to construct cellular and animal models of TDP- 43 ALS like aggregation. Using these models drugs that can revert aggregation and recover function have been identified. Finally, ALS is a disease that occurs mostly during the fifth to the seventh decade of life. In this respect, it has been observed that the onset of the locomotion defect in an ALS fly model coincides with an age-related 4-fold drop in TBPH levels (the Drosophila TDP43 orthologous), similar TDP 43 reduction with age was observed in mice brain. Thus, understanding the relationship between aging and TDP-43 production and mis-folding in cell culture, animal models, and human tissues might provide further clues to explain the time of disease onset. http://sedici.unlp.edu.ar:80/handle/10915/125645 Revision Physiological Mini Reviews; vol. 10, no. 5 Neutrophil extracellular traps (NETs) are web-like structures composed by a chromatin backbone, histones and antimicrobial proteins. NETs constitute yet another mechanism deployed by neutrophils to immobilise and kill microorganisms, thus contributing to the host innate immunity. Neutrophils cast NETs upon stimulation by a variety of stimuli, including bacteria, protozoa, fungi, viruses, their products and also host factors like chemokines, complement and activated platelets. NETs production or NETosis occurs as a result of activation of neutrophil PKC, Raf-MEK-ERK and NADPH oxydase signalling pathways. Driven mostly by peptidylarginine deiminase 4 (PAD4) citrullination of histones, the hallmark of NETosis is chromatin decondensation, rupture of nuclear membrane and release of nuclear and granular contents into the cytoplasm, prior their release into the extracellular space. NETs control propagation of pathogens by entrapping them within the lose chromatin web and kills them with the antimicrobial molecules –granule proteins and histones- present in high concentrations within the chromatin network. Despite contributing to host defence, aberrant NET formation may damage tissues and activate inflammatory cells, contributing to several pathologies, including sepsis, systemic inflammatory response syndrome, autoimmune diseases and thrombosis. This review presents an overview of our current knowledge of NETs physiology and their role in fighting and propagating disease. Sun, 01 Oct 2017 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/125645 2017-10-01T00:00:00Z Neutrophil extracellular traps (NETs) are web-like structures composed by a chromatin backbone, histones and antimicrobial proteins. NETs constitute yet another mechanism deployed by neutrophils to immobilise and kill microorganisms, thus contributing to the host innate immunity. Neutrophils cast NETs upon stimulation by a variety of stimuli, including bacteria, protozoa, fungi, viruses, their products and also host factors like chemokines, complement and activated platelets. NETs production or NETosis occurs as a result of activation of neutrophil PKC, Raf-MEK-ERK and NADPH oxydase signalling pathways. Driven mostly by peptidylarginine deiminase 4 (PAD4) citrullination of histones, the hallmark of NETosis is chromatin decondensation, rupture of nuclear membrane and release of nuclear and granular contents into the cytoplasm, prior their release into the extracellular space. NETs control propagation of pathogens by entrapping them within the lose chromatin web and kills them with the antimicrobial molecules –granule proteins and histones- present in high concentrations within the chromatin network. Despite contributing to host defence, aberrant NET formation may damage tissues and activate inflammatory cells, contributing to several pathologies, including sepsis, systemic inflammatory response syndrome, autoimmune diseases and thrombosis. This review presents an overview of our current knowledge of NETs physiology and their role in fighting and propagating disease. http://sedici.unlp.edu.ar:80/handle/10915/104363 Articulo Physiological Mini Reviews; vol. 10, no. 4 Myocardial stretch induces a two-phase increase in developed force. The first phase occurs immediately, is due to an increase in myofilament Ca2+ responsiveness, and is the expression of the Frank-Starling mechanism. The second phase, gradually developed, results from an increase in intracellular Ca2+ concentration and is known as ?slow force response? (SFR) to stretch. Characterization of the subcellular basis of the increase in Ca2+ responsible for the SFR development was an important objective of our laboratory group during last two decades. We have compiled enough evidence to suggest that the SFR is the mechanical expression of an autocrine/paracrine loop of intracellular signals leading to the reactive oxygen species (ROS)-mediated activation of redox-sensitive kinases that activate (phosphorylate) the cardiac Na+/H+ exchanger (NHE1), increasing intracellular Na+, and consequently, Ca2+ concentration. Recently, we demonstrated that mineralocorticoid receptor (MR) activation after stretch is critical for the progression of this complex signaling pathway. Interestingly, clinical evidence assigns a detrimental role to MR activation in the pathophysiology of heart failure (HF), in which cardiac wall stretch is an important triggering factor. The aim of this mini-review is not only to share our own experience describing novel non-genomic effects of MR activation after acute myocardial stretch and the physiological consequences, but also to discuss other possible pathophysiological implications, as well as the potential clinical impact of this important discovery. Tue, 01 Aug 2017 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/104363 2017-08-01T00:00:00Z Myocardial stretch induces a two-phase increase in developed force. The first phase occurs immediately, is due to an increase in myofilament Ca2+ responsiveness, and is the expression of the Frank-Starling mechanism. The second phase, gradually developed, results from an increase in intracellular Ca2+ concentration and is known as ?slow force response? (SFR) to stretch. Characterization of the subcellular basis of the increase in Ca2+ responsible for the SFR development was an important objective of our laboratory group during last two decades. We have compiled enough evidence to suggest that the SFR is the mechanical expression of an autocrine/paracrine loop of intracellular signals leading to the reactive oxygen species (ROS)-mediated activation of redox-sensitive kinases that activate (phosphorylate) the cardiac Na+/H+ exchanger (NHE1), increasing intracellular Na+, and consequently, Ca2+ concentration. Recently, we demonstrated that mineralocorticoid receptor (MR) activation after stretch is critical for the progression of this complex signaling pathway. Interestingly, clinical evidence assigns a detrimental role to MR activation in the pathophysiology of heart failure (HF), in which cardiac wall stretch is an important triggering factor. The aim of this mini-review is not only to share our own experience describing novel non-genomic effects of MR activation after acute myocardial stretch and the physiological consequences, but also to discuss other possible pathophysiological implications, as well as the potential clinical impact of this important discovery. http://sedici.unlp.edu.ar:80/handle/10915/101276 Articulo Physiological Mini Review; vol. 10, no. 2 Calorimetry has been applied to skeletal and cardiac muscle from many years ago, andthere were intents to calculate the heat fractions associated to basal metabolism (restingheat rate, Hr) and the active heat (Ha). This review explains the principles and evolution of cardiac energetic, measured by calorimetry and the advantages with respect to the measurement of oxygen consumption. Moreover, the methods to estimate separately the fractions of tension-dependent (TDH) and tension-independent heat (TIH) were described, as well as the characterization of each one. A method to determine 4 heat components in a single beat in the presence of contraction in perfused rat ventricles was revised, as well as the properties of the long-duration fourth fraction not previously seen with other methods.The advantages and limitations of each method were analyzed. Calorimetry allows toevaluate the occurrence degree of certain exothermic processes such as ionic fluxes can be studied by comparing the heat released with the energetic equivalent and the stoichiometry of the process with the ATP hydrolysis. Calorimetry is a sensitive and useful methodology to evaluate the "in situ" incidence of exothermic mechanisms in the heart. Sat, 01 Apr 2017 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/101276 2017-04-01T00:00:00Z Calorimetry has been applied to skeletal and cardiac muscle from many years ago, andthere were intents to calculate the heat fractions associated to basal metabolism (restingheat rate, Hr) and the active heat (Ha). This review explains the principles and evolution of cardiac energetic, measured by calorimetry and the advantages with respect to the measurement of oxygen consumption. Moreover, the methods to estimate separately the fractions of tension-dependent (TDH) and tension-independent heat (TIH) were described, as well as the characterization of each one. A method to determine 4 heat components in a single beat in the presence of contraction in perfused rat ventricles was revised, as well as the properties of the long-duration fourth fraction not previously seen with other methods.The advantages and limitations of each method were analyzed. Calorimetry allows toevaluate the occurrence degree of certain exothermic processes such as ionic fluxes can be studied by comparing the heat released with the energetic equivalent and the stoichiometry of the process with the ATP hydrolysis. Calorimetry is a sensitive and useful methodology to evaluate the "in situ" incidence of exothermic mechanisms in the heart. http://sedici.unlp.edu.ar:80/handle/10915/101003 Revision Physiological Mini Reviews; vol. 10, no. 3 This review describes the application of calorimetry to study cardiac energetics in physiological, pharmacological and pathophysiological conditions of a perfused heart preparation. In particular, the factors influencing the resting heat rate (Hr), such asspecies differences among rat, mouse and guinea-pig hearts, as well as the mechanismsunderlying the increased resting heat rate under a high [K+]-cardioplegia were discussed. Our results give support to a functional interaction between the sarcoplasmic reticulum and mitochondria for myocardial Ca2+ movements. Finally, it is briefly commented the application of calorimetry to study Ca2+ homeostasis during a model of stunning induced by no-flow ischemia and reperfusion in entire hearts by usingselective inhibitors of cellular Ca2+ transporters. Either in the presence or absence ofperfusion, calorimetry allows to evaluate the total muscle economy. As application, calorimetry allows to detect a cardiac dysfunction still under unaltered contractility, demonstrating that it is a very sensitive methodology for studying pathological situations and pharmacological consequences. Tue, 01 Aug 2017 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/101003 2017-08-01T00:00:00Z This review describes the application of calorimetry to study cardiac energetics in physiological, pharmacological and pathophysiological conditions of a perfused heart preparation. In particular, the factors influencing the resting heat rate (Hr), such asspecies differences among rat, mouse and guinea-pig hearts, as well as the mechanismsunderlying the increased resting heat rate under a high [K+]-cardioplegia were discussed. Our results give support to a functional interaction between the sarcoplasmic reticulum and mitochondria for myocardial Ca2+ movements. Finally, it is briefly commented the application of calorimetry to study Ca2+ homeostasis during a model of stunning induced by no-flow ischemia and reperfusion in entire hearts by usingselective inhibitors of cellular Ca2+ transporters. Either in the presence or absence ofperfusion, calorimetry allows to evaluate the total muscle economy. As application, calorimetry allows to detect a cardiac dysfunction still under unaltered contractility, demonstrating that it is a very sensitive methodology for studying pathological situations and pharmacological consequences.