Aging-associated Alteration in the Cardiac MIF-AMPK Cascade in Response to Ischemic Stress

An important role for a macrophage migration inhibitory factor (MIF)-AMP-activated protein kinase (AMPK) signaling pathway in ameliorating myocardial damage following ischemia/reperfusion has been described. An aging-associated reduction in AMPK activity may be associated with a decline in the ability of cardiac cells to activate the MIF-AMPK cascade, thereby resulting in reduced tolerance to ischemic insults. To test this hypothesis, _in vivo_ regional ischemia was induced by occlusion of the left anterior descending (LAD) coronary artery in young (4-6 months) and aged (24-26 months) mice. The ischemic AMPK activation response was impaired in aged hearts compared to young ones (p<0.01). Notably, cardiac MIF expression in aged hearts was lower than in young hearts (p<0.01). Dual staining data clearly demonstrated larger infarct size in aged hearts following ischemia and reperfusion compared to young hearts (p<0.05). Ischemia-induced AMPK activation in MIF knock out (MIF KO) hearts was blunted, leading to greater contractile dysfunction of MIF KO cardiomyocytes during hypoxia than that of wild type (WT) cardiomyocytes. Finally exogenous recombinant MIF significantly reversed the contractile dysfunction of aged cardiomyocytes in response to hypoxia. We conclude that an aging-associated reduction in ischemic AMPK activation contributes to ischemic intolerance in aged hearts

Circuito de Granulación de Urea: Análisis de Diagramas de Flujo Alternativos

En este trabajo se utiliza un simulador del circuito de granulación de urea, previamente desarrollado, para explorar diagramas de flujo alternativos al tradicional. La planta de granulación en estudio incluye un granulador de lecho fluidizado, una unidad de enfriamiento, zarandas vibratorias de doble paño y molinos de rodillos. Con las nuevas configuraciones se busca disminuir la cantidad de finos que circulan en el sistema mediante la purga o derivación a disolución de fracciones o la totalidad de la corriente que abandona el molino de rodillos. El análisis de las distintas opciones permitió determinar que la incorporación de una zaranda a la salida de dicho equipo que separe las partículas menores a 1 mm evitando o disminuyendo su ingreso al granulador, favorece la generación de producto dentro del rango de comercialización.Fil: Cotabarren, Ivana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Bucala, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Piña, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin

Lack of macrophage migration inhibitory factor in mice does not affect hallmarks of the inflammatory/immune response during the first week after stroke

<p>Abstract</p> <p>Background</p> <p>Macrophage migration inhibitory factor (MIF) has been proposed to play a detrimental role in stroke. We recently showed that MIF promotes neuronal death and aggravates neurological deficits during the first week after experimental stroke, in mice. Since MIF regulates tissue inflammation, we studied the putative role of MIF in post-stroke inflammation.</p> <p>Methods</p> <p>We subjected C57BL/6 mice, <it>Mif</it>^-/-(MIF-KO) or <it>Mif</it>^+/+(WT), to a transient occlusion of the right middle cerebral artery (tMCAo) or sham-surgery. We studied MIF expression, GFAP expression and the number of CD74-positive cells in the ischemic brain hemisphere 7 days after tMCAo using primarily immunohistochemistry. We determined IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-12, KC/CXCL-1 and TNF-α protein levels in the brain (48 h after surgery) and serum (48 h and 7 days after surgery) by a multiplex immunoassay.</p> <p>Results</p> <p>We observed that MIF accumulates in neurons and astrocytes of the peri-infarct region, as well as in microglia/macrophages of the infarct core up to 7 days after stroke. Among the inflammatory mediators analyzed, we found a significant increase in cerebral IL-12 and KC levels after tMCAo, in comparison to sham-surgery. Importantly, the deletion of <it>Mif </it>did not significantly affect the levels of the cytokines evaluated, in the brain or serum. Moreover, the spleen weight 48 h and 7 days subsequent to tMCAo was similar in WT and MIF-KO mice. Finally, the extent of GFAP immunoreactivity and the number of MIF receptor (CD74)-positive cells within the ischemic brain hemisphere did not differ significantly between WT and MIF-KO mice subjected to tMCAo.</p> <p>Conclusions</p> <p>We conclude that MIF does not affect major components of the inflammatory/immune response during the first week after experimental stroke. Based on present and previous evidence, we propose that the deleterious MIF-mediated effects in stroke depend primarily on an intraneuronal and/or interneuronal action.</p

A coupled atomization-spray drift model as online support tool for boom spray applications

The effectiveness of agrochemical products strongly depends on the capability of the atomized droplets to reach the target site in the desired amount. Spray drift is the movement of droplets downwind of the target area, and its minimization is a growing concern to ensure operator health, protect the environment, achieve efficient crop protection and transform the spraying of phytosanitary products into a sustainable activity. In this contribution, a coupled atomization-spray drift model suitable for different types of nozzles is developed and validated against experimental data. Particularly, the article focuses on providing a simple simulation tool, based on a minimum number of input data that are easily accessable to predict the ground deposition spray drift of a nozzle. It was found that the atomized droplets size distribution can be accurately predicted just as a function of the median volumetric diameter, which was successfully estimated as a function of spray pressure, nozzle nominal flowrate and spray angle (commonly known data). Besides, the proposed model, based on bivariate probability density functions, is able to accurately represent different physical phenomena using a low number of calculations. Its implementation is possible using low-resource computing systems as required for sprayer on-board software tools.Fil: Renaudo, Carlos Alberto. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Bertin, Diego Esteban. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Bucala, Veronica. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin

A hybrid Lagrangian-dispersion model for spray drift prediction applied to horizontal boom sprayers

A spray drift model for horizontal boom sprayers was developed, based on an earlier single nozzle model described by Renaudo et al. (2022). The extended model, which also includes droplets dispersion in the vertical direction, was successfully calibrated and then validated with field data from sources that covers different process conditions. In fact, the calculated spray drift values showed good agreement with reported measurements in a wide range of distances in the downwind direction. For the studied cases, the eddy diffusivity was found to be a function of the relative humidity. In the absence of dispersion-related data, the fitted equation can be used to fully predict spray drift from horizontal boom sprayers. The results indicated that, as the downwind distance increases, more nozzles contribute to the deposited flowrate and therefore accounting for them is necessary for a good representation of the spray drift. The model demonstrated to have low computational costs (time and resources) being then suitable to be used on board sprayer computers and web servers.Fil: Renaudo, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Bertin, Diego Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Bucala, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin

Parabiosis and single-cell RNA sequencing reveal a limited contribution of monocytes to myofibroblasts in kidney fibrosis

Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells, including mesenchymal stem cells, macrophages, and fibrocytes, to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium, we confirm that the proximal tubule does not contribute to the myofibroblast pool. However, in parabiosis models in which one parabiont is genetically labeled and the other is unlabeled and undergoes kidney fibrosis, we demonstrate that a small fraction of genetically labeled renal myofibroblasts derive from the circulation. Single-cell RNA sequencing confirms this finding but indicates that these cells are circulating monocytes, express few extracellular matrix or other myofibroblast genes, and express many proinflammatory cytokines. We conclude that this small circulating myofibroblast progenitor population contributes to renal fibrosis by paracrine rather than direct mechanisms

Increased fructose 2,6-bisphosphate in peripheral blood mononuclear cells of patients with diabetes

Fructose 2,6-bisphosphate (F2,6BP) is a powerful allosteric activator of 6-phosphofructo-1-kinase, which is the rate-limiting enzyme for glycolysis. Mitogenic stimulation of lymphocytes is related to an enhanced rate of glucose utilization and F2,6BP mediated activation of glycolysis. To determine the effect of hyperglycemia on intracellular glycolysis of lymphocytes, we measured intracellular F2,6BP content in peripheral blood mononuclear cells obtained from patients with diabetes and normal subjects. A total of 62 subjects participated in the present study. Venous blood samples were collected and peripheral blood mononuclear cells were separated by Ficoll gradients. Intracellular F2,6BP levels in peripheral blood mononuclear cells from normal control subjects were significantly lower than age-matched diabetic subjects. We observed a significant positive correlation between intracellular F2,6BP levels and long term glycemic control, as assessed by HbA1c. These data suggest that hyperglycemia increases intracellular F2,6BP in immune cells. These findings may help to clarify the impaired function in immune cells in patients with diabetes

MIF contributes to Trypanosoma brucei associated immunopathogenicity development

African trypanosomiasis is a chronic debilitating disease affecting the health and economic well-being of many people in developing countries. The pathogenicity associated with this disease involves a persistent inflammatory response, whereby M1-type myeloid cells, including Ly6C(high) inflammatory monocytes, are centrally implicated. A comparative gene analysis between trypanosusceptible and trypanotolerant animals identified MIF (macrophage migrating inhibitory factor) as an important pathogenic candidate molecule. Using MIF-deficient mice and anti-MIF antibody treated mice, we show that MIF mediates the pathogenic inflammatory immune response and increases the recruitment of inflammatory monocytes and neutrophils to contribute to liver injury in Trypanosoma brucei infected mice. Moreover, neutrophil-derived MIF contributed more significantly than monocyte-derived MIF to increased pathogenic liver TNF production and liver injury during trypanosome infection. MIF deficient animals also featured limited anemia, coinciding with increased iron bio-availability, improved erythropoiesis and reduced RBC clearance during the chronic phase of infection. Our data suggest that MIF promotes the most prominent pathological features of experimental trypanosome infections (i.e. anemia and liver injury), and prompt considering MIF as a novel target for treatment of trypanosomiasis-associated immunopathogenicity

Caracterización de tamaños de partícula: comparación entre difracción laser (ld) y microscopía electrónica de barrido (sem)

Two of the most significant properties of particles are size and shape; they often have direct influence on the materials behavior. Since the particulate systems are constituted by 3D particles of different size, the characterization of this property has to be given by a particle size distribution (PSD) . Among the most popular techniques for PSDs measurement, the image analysis (IA) presents some disadvantages: sampling errors, the analysis of only hundred or a few thousand particles to represent the whole population, the use a 2-D projected image of a 3-D particle and long analysis times. In contrast, the laser diffraction technique allows fast particulate systems characterization, processes a high number of particles per assay and provides highly reproducible results. However, LD provides no details about the particle morphology. Both techniques can be considered complementary, however several data interpretation problems appear whe n the results are compared. To do so, it is necessary to understand the meaning of the size descriptors given by each technique and under which conditions the comparison of results from different size analyzers can be done. In this sense, this work explores first the number of particles required to obtain reproducible PSDs by SEM. Then, it presents a comprehensive characterization of PVC particles by assessing a set of size and shape descriptors. The PSDs obtained by IA-SEM and LD were mathematically transformed to be compared. Finally, IA-SEM data was used to evaluate the convenience of using more than one size descriptor to represent the particles volume.Fil: Hegel, C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Planta Piloto de Ingeniería Química (i); ArgentinaFil: Jones, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahia Blanca; ArgentinaFil: Cabrera, Fernanda Anabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Planta Piloto de Ingeniería Química (i); ArgentinaFil: Yañez, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahia Blanca; ArgentinaFil: Bucala, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Planta Piloto de Ingeniería Química (i); Argentin