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Papers by Antonella Pantaleo

International Journal of Molecular Sciences, Apr 24, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Redox biology, Sep 1, 2020

Fyn is a tyrosine kinase belonging to the Src family (Src-Family-Kinase, SFK), ubiquitously expre... more Fyn is a tyrosine kinase belonging to the Src family (Src-Family-Kinase, SFK), ubiquitously expressed. Previously, we report that Fyn is important in stress erythropoiesis. Here, we show that in red cells Fyn specifically stimulates G6PD activity, resulting in a 3-fold increase enzyme catalytic activity (k cat) by phosphorylating tyrosine (Tyr)-401. We found Tyr-401 on G6PD as functional target of Fyn in normal human red blood cells (RBC), being undetectable in G6PD deficient RBCs (G6PD-Mediterranean and G6PD-Genova). Indeed, Tyr-401 is located to a region of the G6PD molecule critical for the formation of the enzymatically active dimer. Amino acid replacements in this region are mostly associated with a chronic hemolysis phenotype. Using mutagenesis approach, we demonstrated that the phosphorylation status of Tyr401 modulates the interaction of G6PD with G6P and stabilizes G6PD in a catalytically more efficient conformation. RBCs from Fyn-/À mice are defective in G6PD activity, resulting in increased susceptibility to primaquine-induced intravascular hemolysis. This negatively affected the recycling of reduced Prx2 in response to oxidative stress, indicating that defective G6PD phosphorylation impairs defense against oxidation. In human RBCs, we confirm the involvement of the thioredoxin/Prx2 system in the increase vulnerability of G6PD deficient RBCs to oxidation. In conclusion, our data suggest that Fyn is an oxidative radical sensor, and that Fyn-mediated Tyr-401 phosphorylation, by increasing G6PD activity, plays an important role in the physiology of RBCs. Failure of G6PD activation by this mechanism may be a major limiting factor in the ability of G6PD deficient RBCs to withstand oxidative stress.

Frontiers in space technologies, Jul 19, 2023

sunlight absorbers in architectures with a cavity-like solar receiver. Finally, a new study is re... more sunlight absorbers in architectures with a cavity-like solar receiver. Finally, a new study is reported which combines biochemical and biophysical approaches in order to compare, under simulated microgravity and under terrestrial conditions, the functioning and structure of red blood cells, over various intervals of time.

Journal of biological research, Nov 8, 2022

PLOS ONE

Nowadays, fungal infections increase, and the demand of novel antifungal agents is constantly ris... more Nowadays, fungal infections increase, and the demand of novel antifungal agents is constantly rising. In the present study, silver, titanium dioxide, cobalt (II) hydroxide and cobalt (II,III) oxide nanomaterials have been synthesized from Spirulina platensis extract. The synthesis mechanism has been studied using GCMS and FTIR thus confirming the involvement of secondary metabolites, mainly amines. The obtained products have been analysed using XRD, SEM, TGA and zeta potential techniques. The findings revealed average crystallite size of 15.22 nm with 9.72 nm for oval-shaped silver nanoparticles increasing to 26.01 nm and 24.86 nm after calcination and 4.81 nm for spherical-shaped titanium dioxide nanoparticles which decreased to 4.62 nm after calcination. Nanoflake shape has been observed for cobalt hydroxide nanomaterials and for cobalt (II, III) oxide with crystallite size of 3.52 nm and 13.28 nm, respectively. Silver nanoparticles showed the best thermal and water dispersion sta...

International Journal of Molecular Sciences

Lipidomics and metabolomics are nowadays widely used to provide promising insights into the patho... more Lipidomics and metabolomics are nowadays widely used to provide promising insights into the pathophysiology of cellular stress disorders. Our study expands, with the use of a hyphenated ion mobility mass spectrometric platform, the understanding of the cellular processes and stress due to microgravity. By lipid profiling of human erythrocytes, we annotated complex lipids such as oxidized phosphocholines, phosphocholines bearing arachidonic in their moiety, as well as sphingomyelins and hexosyl ceramides associated with microgravity conditions. Overall, our findings give an insight into the molecular alterations and identify erythrocyte lipidomics signatures associated with microgravity conditions. If the present results are confirmed in future studies, they may help to develop suitable treatments for astronauts after return to Earth.

International Journal of Molecular Sciences

Alzheimer’s disease (AD) is characterized by an initial accumulation of amyloid plaques and neuro... more Alzheimer’s disease (AD) is characterized by an initial accumulation of amyloid plaques and neurofibrillary tangles, along with the depletion of cholinergic markers. The currently available therapies for AD do not present any disease-modifying effects, with the available in vitro platforms to study either AD drug candidates or basic biology not fully recapitulating the main features of the disease or being extremely costly, such as iPSC-derived neurons. In the present work, we developed and validated a novel cell-based AD model featuring Tau hyperphosphorylation and degenerative neuronal morphology. Using the model, we evaluated the efficacy of three different groups of newly synthesized acetylcholinesterase (AChE) inhibitors, along with a new dual acetylcholinesterase/glycogen synthase kinase 3 inhibitor, as potential AD treatment on differentiated SH-SY5Y cells treated with glyceraldehyde to induce Tau hyperphosphorylation, and subsequently neurite degeneration and cell death. Tes...

International Journal of Molecular Sciences

Erythrocytes are highly specialized cells in human body, and their main function is to ensure the... more Erythrocytes are highly specialized cells in human body, and their main function is to ensure the gas exchanges, O2 and CO2, within the body. The exposure to microgravity environment leads to several health risks such as those affecting red blood cells. In this work, we investigated the changes that occur in the structure and function of red blood cells under simulated microgravity, compared to terrestrial conditions, at different time points using biochemical and biophysical techniques. Erythrocytes exposed to simulated microgravity showed morphological changes, a constant increase in reactive oxygen species (ROS), a significant reduction in total antioxidant capacity (TAC), a remarkable and constant decrease in total glutathione (GSH) concentration, and an augmentation in malondialdehyde (MDA) at increasing times. Moreover, experiments were performed to evaluate the lipid profile of erythrocyte membranes which showed an upregulation in the following membrane phosphocholines (PC): ...

The Journal of Infectious Diseases, 2019

BackgroundHemoglobin (Hb) data are limited in Southeast Asian glucose-6-phosphate dehydrogenase (... more BackgroundHemoglobin (Hb) data are limited in Southeast Asian glucose-6-phosphate dehydrogenase (G6PD) deficient (G6PD−) patients treated weekly with the World Health Organization–recommended primaquine regimen (ie, 0.75 mg/kg/week for 8 weeks [PQ 0.75]).MethodsWe treated Cambodians who had acute Plasmodium vivax infection with PQ0.75 and a 3-day course of dihydroartemisinin/piperaquine and determined the Hb level, reticulocyte count, G6PD genotype, and Hb type.ResultsSeventy-five patients (male sex, 63) aged 5–63 years (median, 24 years) were enrolled. Eighteen were G6PD deficient (including 17 with G6PD Viangchan) and 57 were not G6PD deficient; 26 had HbE (of whom 25 were heterozygous), and 6 had α-/β-thalassemia. Mean Hb concentrations at baseline (ie, day 0) were similar between G6PD deficient and G6PD normal patients (12.9 g/dL [range, 9‒16.3 g/dL] and 13.26 g/dL [range, 9.6‒16 g/dL], respectively; P = .46). G6PD deficiency (P = <.001), higher Hb concentration at baseline (...

The Journal of Infection in Developing Countries, 2012

Introduction: We propose a new method for the selective labeling, isolation and electrophoretic a... more Introduction: We propose a new method for the selective labeling, isolation and electrophoretic analysis of the Plasmodium falciparum protein exposed on the erythrocyte cell surface. Historically, membrane surface proteins have been isolated using a surface biotinylation followed by capture of biotin-conjugated protein via an avidin/streptavidin-coated solid support. The major drawback of the standard methods has been the labeling of internal proteins due to fast internalization of biotin. Methodology: To solve this problem, we used a biotin label that does not permeate through the membrane. As a further precaution to avoid the purification of non surface exposed proteins, we directly challenged whole labeled cells with avidin coated beads and then solubilized them using non ionic detergents. Results: A marked enrichment of most of the RBC membrane proteins known to face the external surface of the membrane validated the specificity of the method; furthermore, only small amounts of ...

Marine Drugs

Spirulina is the most studied cyanobacterium species for both pharmacological applications and th... more Spirulina is the most studied cyanobacterium species for both pharmacological applications and the food industry. The aim of the present review is to summarize the potential benefits of the use of Spirulina for improving healthcare both in space and on Earth. Regarding the first field of application, Spirulina could represent a new technology for the sustainment of long-duration manned missions to planets beyond the Lower Earth Orbit (e.g., Mars); furthermore, it could help astronauts stay healthy while exposed to a variety of stress factors that can have negative consequences even after years. As far as the second field of application, Spirulina could have an active role in various aspects of medicine, such as metabolism, oncology, ophthalmology, central and peripheral nervous systems, and nephrology. The recent findings of the capacity of Spirulina to improve stem cells mobility and to increase immune response have opened new intriguing scenarios in oncological and infectious dise...

Blood, 2017

In companion papers [1, 2], we have discussed current bounds of a new super-light baryo-photon, a... more In companion papers [1, 2], we have discussed current bounds of a new super-light baryo-photon, associated to a U (1)B−L gauged, from neutron-antineutron current data, which are competitive with Eötvös type experiments. Here, we discuss the implications of a possible baryo-photon detection in string theory and quantum gravity. The discovery of a very light gauge boson should imply the violation of the Weak Gravity Conjecture, carrying deep consequences in our understanding of holography, quantum gravity and black holes. On the other hand, we show how the detection of a baryo-photon would also exclude the generation of all B−L violating operators from Exotic Stringy Instantons. We will disclaim the common statement in literature that neutron-antineutron may indirectly test at least a 300 − 1000 TeV scale. Searches of baryo-photons can provide indirect informations of the Planck (or String) scale (quantum black holes, holography and non-perturbative stringy effects). This strongly motivates new neutron-antineutron experiments with adjustable magnetic fields dedicated to the detection of super-light baryo-photons.

Microcirculation, 2013

The control of arteriolar diameters in microvasculature has been in the focus of studies on mecha... more The control of arteriolar diameters in microvasculature has been in the focus of studies on mechanisms matching oxygen demand and supply at the tissue level. Functionally, important vascular elements include EC, VSMC, and RBC. Integration of these different cell types into functional units aimed at matching tissue oxygen supply with tissue oxygen demand is only achieved when all these cells can respond to the signals of tissue oxygen demand. Many vasoactive agents that serve as signals of tissue oxygen demand have their receptors on all these types of cells (VSMC, EC, and RBC) implying that there can be a coordinated regulation of their behavior by the tissue oxygen demand. Such functions of RBC as oxygen carrying by Hb, rheology, and release of vasoactive agents are considered. Several common extra- and intracellular signaling pathways that link tissue oxygen demand with control of VSMC contractility, EC permeability, and RBC functioning are discussed.

Current Organic Chemistry, 2015

ABSTRACT

Journal of Experimental Medicine, 2021

To egress from its erythrocyte host, the malaria parasite, Plasmodium falciparum, must destabiliz... more To egress from its erythrocyte host, the malaria parasite, Plasmodium falciparum, must destabilize the erythrocyte membrane by activating an erythrocyte tyrosine kinase. Because imatinib inhibits erythrocyte tyrosine kinases and because imatinib has a good safety profile, we elected to determine whether coadministration of imatinib with standard of care (SOC) might be both well tolerated and therapeutically efficacious in malaria patients. Patients with uncomplicated P. falciparum malaria from a region in Vietnam where one third of patients experience delayed parasite clearance (DPC; continued parasitemia after 3 d of therapy) were treated for 3 d with either the region’s SOC (40 mg dihydroartemisinin + 320 mg piperaquine/d) or imatinib (400 mg/d) + SOC. Imatinib + SOC–treated participants exhibited no increase in number or severity of adverse events, a significantly accelerated decline in parasite density and pyrexia, and no DPC. Surprisingly, these improvements were most pronounce...

Cellular and Molecular Bioengineering, 2020

Approximating a real manifold by an idealized one requires to calibrate the parameters characteri... more Approximating a real manifold by an idealized one requires to calibrate the parameters characterizing the idealized manifold in function of the real one. This calibration is a purely conventional process and can generally be done in several ways, leading to different fittings. In practice, however, all possible fittings cannot be considered as representative of the real manifold. Approximating the real metric of the universe by the FLRW metric would be adequate only if both corresponding structures, defined by the space-time interval, are equivalent on large scales. This requirement puts some constraints on what would be a representative FLRW metric. We show that the way how measurements on SNIa are interpreted to determine the evolution of the scale factor implicitly define the calibration process, and that this one is compatible with the aforementioned constraints. On a theoretical point of view, this indicates that the as fitted FLRW metric would indeed be representative of the real one. On a practical point of view, however, we show that a bias in the measurements could invalidate this conclusion. The bias comes from the fact that SNIa are not randomly distributed over space, but are probably mostly located in regions were matter is largely present, i.e., in overdense regions. We explain how this bias could account for the apparent accelerated expansion of the universe, without needing to introduce the dark energy assumption. We show in particular that this bias leads to an inadequate fitting of the FLRW metric, resulting in the appearance of a new term in the evolution equation of the related scale factor, being equivalent to the cosmological constant.

The Journal of Infectious Diseases, 2019

PloS one, 2018

Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized ... more Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs) and an increase in the percentage of surviving parasites. The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure. Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P. falciparum Palo Alto (PA) cultures with sub-lethal concentrations of dihydroartemisinin (DHA). The resistance phenotype was maintained for over 1 year through monthly maintenance treatments with low doses of 2.5 nM DHA. There was a moderate increase in the DHA IC50 in ARS1 when compared with parental strain PA after 72 h of drug exposure (from 0.68 nM to 2 nM DHA). In...

International Journal of Molecular Sciences, Apr 24, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Redox biology, Sep 1, 2020

Fyn is a tyrosine kinase belonging to the Src family (Src-Family-Kinase, SFK), ubiquitously expre... more Fyn is a tyrosine kinase belonging to the Src family (Src-Family-Kinase, SFK), ubiquitously expressed. Previously, we report that Fyn is important in stress erythropoiesis. Here, we show that in red cells Fyn specifically stimulates G6PD activity, resulting in a 3-fold increase enzyme catalytic activity (k cat) by phosphorylating tyrosine (Tyr)-401. We found Tyr-401 on G6PD as functional target of Fyn in normal human red blood cells (RBC), being undetectable in G6PD deficient RBCs (G6PD-Mediterranean and G6PD-Genova). Indeed, Tyr-401 is located to a region of the G6PD molecule critical for the formation of the enzymatically active dimer. Amino acid replacements in this region are mostly associated with a chronic hemolysis phenotype. Using mutagenesis approach, we demonstrated that the phosphorylation status of Tyr401 modulates the interaction of G6PD with G6P and stabilizes G6PD in a catalytically more efficient conformation. RBCs from Fyn-/À mice are defective in G6PD activity, resulting in increased susceptibility to primaquine-induced intravascular hemolysis. This negatively affected the recycling of reduced Prx2 in response to oxidative stress, indicating that defective G6PD phosphorylation impairs defense against oxidation. In human RBCs, we confirm the involvement of the thioredoxin/Prx2 system in the increase vulnerability of G6PD deficient RBCs to oxidation. In conclusion, our data suggest that Fyn is an oxidative radical sensor, and that Fyn-mediated Tyr-401 phosphorylation, by increasing G6PD activity, plays an important role in the physiology of RBCs. Failure of G6PD activation by this mechanism may be a major limiting factor in the ability of G6PD deficient RBCs to withstand oxidative stress.

Frontiers in space technologies, Jul 19, 2023

sunlight absorbers in architectures with a cavity-like solar receiver. Finally, a new study is re... more sunlight absorbers in architectures with a cavity-like solar receiver. Finally, a new study is reported which combines biochemical and biophysical approaches in order to compare, under simulated microgravity and under terrestrial conditions, the functioning and structure of red blood cells, over various intervals of time.

Journal of biological research, Nov 8, 2022

PLOS ONE

Nowadays, fungal infections increase, and the demand of novel antifungal agents is constantly ris... more Nowadays, fungal infections increase, and the demand of novel antifungal agents is constantly rising. In the present study, silver, titanium dioxide, cobalt (II) hydroxide and cobalt (II,III) oxide nanomaterials have been synthesized from Spirulina platensis extract. The synthesis mechanism has been studied using GCMS and FTIR thus confirming the involvement of secondary metabolites, mainly amines. The obtained products have been analysed using XRD, SEM, TGA and zeta potential techniques. The findings revealed average crystallite size of 15.22 nm with 9.72 nm for oval-shaped silver nanoparticles increasing to 26.01 nm and 24.86 nm after calcination and 4.81 nm for spherical-shaped titanium dioxide nanoparticles which decreased to 4.62 nm after calcination. Nanoflake shape has been observed for cobalt hydroxide nanomaterials and for cobalt (II, III) oxide with crystallite size of 3.52 nm and 13.28 nm, respectively. Silver nanoparticles showed the best thermal and water dispersion sta...

International Journal of Molecular Sciences

Lipidomics and metabolomics are nowadays widely used to provide promising insights into the patho... more Lipidomics and metabolomics are nowadays widely used to provide promising insights into the pathophysiology of cellular stress disorders. Our study expands, with the use of a hyphenated ion mobility mass spectrometric platform, the understanding of the cellular processes and stress due to microgravity. By lipid profiling of human erythrocytes, we annotated complex lipids such as oxidized phosphocholines, phosphocholines bearing arachidonic in their moiety, as well as sphingomyelins and hexosyl ceramides associated with microgravity conditions. Overall, our findings give an insight into the molecular alterations and identify erythrocyte lipidomics signatures associated with microgravity conditions. If the present results are confirmed in future studies, they may help to develop suitable treatments for astronauts after return to Earth.

International Journal of Molecular Sciences

Alzheimer’s disease (AD) is characterized by an initial accumulation of amyloid plaques and neuro... more Alzheimer’s disease (AD) is characterized by an initial accumulation of amyloid plaques and neurofibrillary tangles, along with the depletion of cholinergic markers. The currently available therapies for AD do not present any disease-modifying effects, with the available in vitro platforms to study either AD drug candidates or basic biology not fully recapitulating the main features of the disease or being extremely costly, such as iPSC-derived neurons. In the present work, we developed and validated a novel cell-based AD model featuring Tau hyperphosphorylation and degenerative neuronal morphology. Using the model, we evaluated the efficacy of three different groups of newly synthesized acetylcholinesterase (AChE) inhibitors, along with a new dual acetylcholinesterase/glycogen synthase kinase 3 inhibitor, as potential AD treatment on differentiated SH-SY5Y cells treated with glyceraldehyde to induce Tau hyperphosphorylation, and subsequently neurite degeneration and cell death. Tes...

International Journal of Molecular Sciences

Erythrocytes are highly specialized cells in human body, and their main function is to ensure the... more Erythrocytes are highly specialized cells in human body, and their main function is to ensure the gas exchanges, O2 and CO2, within the body. The exposure to microgravity environment leads to several health risks such as those affecting red blood cells. In this work, we investigated the changes that occur in the structure and function of red blood cells under simulated microgravity, compared to terrestrial conditions, at different time points using biochemical and biophysical techniques. Erythrocytes exposed to simulated microgravity showed morphological changes, a constant increase in reactive oxygen species (ROS), a significant reduction in total antioxidant capacity (TAC), a remarkable and constant decrease in total glutathione (GSH) concentration, and an augmentation in malondialdehyde (MDA) at increasing times. Moreover, experiments were performed to evaluate the lipid profile of erythrocyte membranes which showed an upregulation in the following membrane phosphocholines (PC): ...

The Journal of Infectious Diseases, 2019

BackgroundHemoglobin (Hb) data are limited in Southeast Asian glucose-6-phosphate dehydrogenase (... more BackgroundHemoglobin (Hb) data are limited in Southeast Asian glucose-6-phosphate dehydrogenase (G6PD) deficient (G6PD−) patients treated weekly with the World Health Organization–recommended primaquine regimen (ie, 0.75 mg/kg/week for 8 weeks [PQ 0.75]).MethodsWe treated Cambodians who had acute Plasmodium vivax infection with PQ0.75 and a 3-day course of dihydroartemisinin/piperaquine and determined the Hb level, reticulocyte count, G6PD genotype, and Hb type.ResultsSeventy-five patients (male sex, 63) aged 5–63 years (median, 24 years) were enrolled. Eighteen were G6PD deficient (including 17 with G6PD Viangchan) and 57 were not G6PD deficient; 26 had HbE (of whom 25 were heterozygous), and 6 had α-/β-thalassemia. Mean Hb concentrations at baseline (ie, day 0) were similar between G6PD deficient and G6PD normal patients (12.9 g/dL [range, 9‒16.3 g/dL] and 13.26 g/dL [range, 9.6‒16 g/dL], respectively; P = .46). G6PD deficiency (P = <.001), higher Hb concentration at baseline (...

The Journal of Infection in Developing Countries, 2012

Introduction: We propose a new method for the selective labeling, isolation and electrophoretic a... more Introduction: We propose a new method for the selective labeling, isolation and electrophoretic analysis of the Plasmodium falciparum protein exposed on the erythrocyte cell surface. Historically, membrane surface proteins have been isolated using a surface biotinylation followed by capture of biotin-conjugated protein via an avidin/streptavidin-coated solid support. The major drawback of the standard methods has been the labeling of internal proteins due to fast internalization of biotin. Methodology: To solve this problem, we used a biotin label that does not permeate through the membrane. As a further precaution to avoid the purification of non surface exposed proteins, we directly challenged whole labeled cells with avidin coated beads and then solubilized them using non ionic detergents. Results: A marked enrichment of most of the RBC membrane proteins known to face the external surface of the membrane validated the specificity of the method; furthermore, only small amounts of ...

Marine Drugs

Spirulina is the most studied cyanobacterium species for both pharmacological applications and th... more Spirulina is the most studied cyanobacterium species for both pharmacological applications and the food industry. The aim of the present review is to summarize the potential benefits of the use of Spirulina for improving healthcare both in space and on Earth. Regarding the first field of application, Spirulina could represent a new technology for the sustainment of long-duration manned missions to planets beyond the Lower Earth Orbit (e.g., Mars); furthermore, it could help astronauts stay healthy while exposed to a variety of stress factors that can have negative consequences even after years. As far as the second field of application, Spirulina could have an active role in various aspects of medicine, such as metabolism, oncology, ophthalmology, central and peripheral nervous systems, and nephrology. The recent findings of the capacity of Spirulina to improve stem cells mobility and to increase immune response have opened new intriguing scenarios in oncological and infectious dise...

Blood, 2017

In companion papers [1, 2], we have discussed current bounds of a new super-light baryo-photon, a... more In companion papers [1, 2], we have discussed current bounds of a new super-light baryo-photon, associated to a U (1)B−L gauged, from neutron-antineutron current data, which are competitive with Eötvös type experiments. Here, we discuss the implications of a possible baryo-photon detection in string theory and quantum gravity. The discovery of a very light gauge boson should imply the violation of the Weak Gravity Conjecture, carrying deep consequences in our understanding of holography, quantum gravity and black holes. On the other hand, we show how the detection of a baryo-photon would also exclude the generation of all B−L violating operators from Exotic Stringy Instantons. We will disclaim the common statement in literature that neutron-antineutron may indirectly test at least a 300 − 1000 TeV scale. Searches of baryo-photons can provide indirect informations of the Planck (or String) scale (quantum black holes, holography and non-perturbative stringy effects). This strongly motivates new neutron-antineutron experiments with adjustable magnetic fields dedicated to the detection of super-light baryo-photons.

Microcirculation, 2013

The control of arteriolar diameters in microvasculature has been in the focus of studies on mecha... more The control of arteriolar diameters in microvasculature has been in the focus of studies on mechanisms matching oxygen demand and supply at the tissue level. Functionally, important vascular elements include EC, VSMC, and RBC. Integration of these different cell types into functional units aimed at matching tissue oxygen supply with tissue oxygen demand is only achieved when all these cells can respond to the signals of tissue oxygen demand. Many vasoactive agents that serve as signals of tissue oxygen demand have their receptors on all these types of cells (VSMC, EC, and RBC) implying that there can be a coordinated regulation of their behavior by the tissue oxygen demand. Such functions of RBC as oxygen carrying by Hb, rheology, and release of vasoactive agents are considered. Several common extra- and intracellular signaling pathways that link tissue oxygen demand with control of VSMC contractility, EC permeability, and RBC functioning are discussed.

Current Organic Chemistry, 2015

ABSTRACT

Journal of Experimental Medicine, 2021

To egress from its erythrocyte host, the malaria parasite, Plasmodium falciparum, must destabiliz... more To egress from its erythrocyte host, the malaria parasite, Plasmodium falciparum, must destabilize the erythrocyte membrane by activating an erythrocyte tyrosine kinase. Because imatinib inhibits erythrocyte tyrosine kinases and because imatinib has a good safety profile, we elected to determine whether coadministration of imatinib with standard of care (SOC) might be both well tolerated and therapeutically efficacious in malaria patients. Patients with uncomplicated P. falciparum malaria from a region in Vietnam where one third of patients experience delayed parasite clearance (DPC; continued parasitemia after 3 d of therapy) were treated for 3 d with either the region’s SOC (40 mg dihydroartemisinin + 320 mg piperaquine/d) or imatinib (400 mg/d) + SOC. Imatinib + SOC–treated participants exhibited no increase in number or severity of adverse events, a significantly accelerated decline in parasite density and pyrexia, and no DPC. Surprisingly, these improvements were most pronounce...

Cellular and Molecular Bioengineering, 2020

Approximating a real manifold by an idealized one requires to calibrate the parameters characteri... more Approximating a real manifold by an idealized one requires to calibrate the parameters characterizing the idealized manifold in function of the real one. This calibration is a purely conventional process and can generally be done in several ways, leading to different fittings. In practice, however, all possible fittings cannot be considered as representative of the real manifold. Approximating the real metric of the universe by the FLRW metric would be adequate only if both corresponding structures, defined by the space-time interval, are equivalent on large scales. This requirement puts some constraints on what would be a representative FLRW metric. We show that the way how measurements on SNIa are interpreted to determine the evolution of the scale factor implicitly define the calibration process, and that this one is compatible with the aforementioned constraints. On a theoretical point of view, this indicates that the as fitted FLRW metric would indeed be representative of the real one. On a practical point of view, however, we show that a bias in the measurements could invalidate this conclusion. The bias comes from the fact that SNIa are not randomly distributed over space, but are probably mostly located in regions were matter is largely present, i.e., in overdense regions. We explain how this bias could account for the apparent accelerated expansion of the universe, without needing to introduce the dark energy assumption. We show in particular that this bias leads to an inadequate fitting of the FLRW metric, resulting in the appearance of a new term in the evolution equation of the related scale factor, being equivalent to the cosmological constant.

The Journal of Infectious Diseases, 2019

PloS one, 2018

Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized ... more Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs) and an increase in the percentage of surviving parasites. The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure. Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P. falciparum Palo Alto (PA) cultures with sub-lethal concentrations of dihydroartemisinin (DHA). The resistance phenotype was maintained for over 1 year through monthly maintenance treatments with low doses of 2.5 nM DHA. There was a moderate increase in the DHA IC50 in ARS1 when compared with parental strain PA after 72 h of drug exposure (from 0.68 nM to 2 nM DHA). In...