Stimulation of S1PR5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington's disease

Huntington's disease (HD) is themost common neurodegenerative disorder for which no effective cure is yet available. Although several agents have been identified to provide benefits so far, the number of therapeutic options remains limited with only symptomatic treatment available. Over the past few years, we have demonstrated that sphingolipid-based approachesmay open the door to newandmore targeted treatments for the disease. In this study, we investigated the therapeutic potential of stimulating sphingosine-1-phosphate (S1P) receptor 5 by the new selective agonist A-971432 (provided by AbbVie) in R6/2mice, a widely used HD animalmodel. Chronic administration of low-dose (0.1mg/kg) A-971432 slowed down the progression of the disease and significantly prolonged lifespan in symptomatic R6/2mice. Such beneficial effects were associated with activation of pro-survival pathways (BDNF, AKT and ERK) and with reduction of mutant huntingtin aggregation. A-971432 also protected blood-brain barrier (BBB) homeostasis in the same mice. Interestingly, when administered early in the disease, before any overt symptoms, A-971432 completely protected HDmice fromthe classic progressivemotor deficit and preserved BBB integrity. Beside representing a promising strategy to take into consideration for the development of alternative therapeutic options for HD, selective stimulation of S1P receptor 5may be also seen as an effective approach to target brain vasculature defects in the disease

Predictive Multi Experiment Approach for the Determination of Conjugated Phenolic Compounds in Vegetal Matrices by Means of LC-MS/MS

Polyphenols (PCs) are a numerous class of bioactive molecules and are known for their antioxidant activity. In this work, the potential of the quadrupole/linear ion trap hybrid mass spectrometer (LIT-QqQ) was exploited to develop a semi-untargeted method for the identification of polyphenols in different food matrices: green coffee, Crocus sativus L. (saffron) and Humulus lupulus L. (hop). Several conjugate forms of flavonoids and hydroxycinnamic acid were detected using neutral loss (NL) as a survey scan coupled with dependent scans with enhanced product ion (EPI) based on information-dependent acquisition (IDA) criteria. The presented approach is focused on a specific class of molecules and provides comprehensive information on the different conjugation models that are related to specific base molecules, thus allowing a quick and effective identification of all possible combinations, such as mono-, di-, or tri-glycosylation or another type of conjugation such as quinic acid esters

Investigation of dark count rate in NbRe microstrips for single photon detection

Superconducting microstrip single photon detectors (SMSPDs) received great interest since they are expected to combine the excellent performance of superconducting nanostrip single photon detectors with the possibility to cover large active areas using low-cost fabrication techniques. In this work, we fabricated SMSPDs based on NbRe to investigate the role of vortices in the dark counts events in this innovative material and in devices with micrometer size. We realized devices with different layouts, namely single microstrips and pairs of parallel microstrips. The energy barriers related to the motion of single vortices or vortex-antivortex pairs, responsible of detection events, have been determined and compared with the ones of similar devices based on different materials, such as MoSi, WSi and NbN. The analysis confirms the high potential of NbRe for the realization of superconducting single photon detectors with large areas

Características productivas de establecimientos en transición agroecológica y diferencias edáficas con productores convencionales

Se estudiaron sistemas familiares de producción en transición agroecológica (SFTA) y sistemas de producción convencionales (SC), de los partidos de Luján, General Rodríguez y San Andrés de Giles. Se determinó en suelo: materia orgánica, fósforo, pH, CE y respiración; el pH y la conductividad presentaron escasas diferencias entre SFTA y SC, en tanto que la materia orgánica, la respiración y el P fueron superiores en SFTA, indicando que sus sistemas podrían ser sustentables a largo plazo. Se realizaron entrevistas y encuestas a los productores sobre sus formas de organización y comercialización: los SFTA poseen escasas superficies, producen leche de vaca Jersey, cabras y venta de terneros. Los SFTA viven en sus establecimientos, comercializan en ferias locales y vecinos. Presentan formas asociativas, expresan respeto por el ambiente y buscan una mayor calidad de sus productos. Los SC presentan grandes extensiones, no viven en el campo y operan con contratistas.Family production systems in agro-ecological transition (SFTA) and neighbors conventional farm system (SC) matches Lujan, General Rodríguez and San André de Giles were studied. It was determined in soil: organic matter, P, pH, EC and breathing; pH and conductivity showed little difference between SFTA and SC, while organic matter, respiration and P were higher in SFTA, indicating that their systems could be sustainable in the long term. Interviews and surveys were made to farmers on their forms of organization and marketing: the SFTA have poor surfaces, produce milk Jersey cows, goats and selling calves. The SFTA live in their establishments, sold at local fairs and neighbors. They express respect for the environment, shows associative forms and seek a better quality of their products. The SC have large areas, they do not live in the field and operate with contractors.Eje: A1 Sistemas de producción de base agroecológica (Trabajos científicos)Facultad de Ciencias Agrarias y Forestale

Características productivas de establecimientos en transición agroecológica y diferencias edáficas con productores convencionales

Se estudiaron sistemas familiares de producción en transición agroecológica (SFTA) y sistemas de producción convencionales (SC), de los partidos de Luján, General Rodríguez y San Andrés de Giles. Se determinó en suelo: materia orgánica, fósforo, pH, CE y respiración; el pH y la conductividad presentaron escasas diferencias entre SFTA y SC, en tanto que la materia orgánica, la respiración y el P fueron superiores en SFTA, indicando que sus sistemas podrían ser sustentables a largo plazo. Se realizaron entrevistas y encuestas a los productores sobre sus formas de organización y comercialización: los SFTA poseen escasas superficies, producen leche de vaca Jersey, cabras y venta de terneros. Los SFTA viven en sus establecimientos, comercializan en ferias locales y vecinos. Presentan formas asociativas, expresan respeto por el ambiente y buscan una mayor calidad de sus productos. Los SC presentan grandes extensiones, no viven en el campo y operan con contratistas.Family production systems in agro-ecological transition (SFTA) and neighbors conventional farm system (SC) matches Lujan, General Rodríguez and San André de Giles were studied. It was determined in soil: organic matter, P, pH, EC and breathing; pH and conductivity showed little difference between SFTA and SC, while organic matter, respiration and P were higher in SFTA, indicating that their systems could be sustainable in the long term. Interviews and surveys were made to farmers on their forms of organization and marketing: the SFTA have poor surfaces, produce milk Jersey cows, goats and selling calves. The SFTA live in their establishments, sold at local fairs and neighbors. They express respect for the environment, shows associative forms and seek a better quality of their products. The SC have large areas, they do not live in the field and operate with contractors.Eje: A1 Sistemas de producción de base agroecológica (Trabajos científicos)Facultad de Ciencias Agrarias y Forestale

Differential expression of sphingolipid metabolizing enzymes in spontaneously hypertensive rats: a possible substrate for susceptibility to brain and kidney damage

Alterations in the metabolism of sphingolipids, a class of biologically active molecules in cell membranes with direct effect on vascular homeostasis, are increasingly recognized as important determinant in different vascular disorders. However, it is not clear whether sphingolipids are implicated in the pathogenesis of hypertension-related cerebrovascular and renal damage. In this study, we evaluated the existence of possible abnormalities related to the sphingolipid metabolism in the brain and kidneys of two well validated spontaneously hypertensive rat strains, the stroke-prone (SHRSP) and the stroke-resistant (SHRSR) models, as compared to the normotensive Wistar Kyoto (WKY) rat strain. Our results showed a global alteration in the metabolism of sphingolipids in both cerebral and renal tissues of both hypertensive strains as compared to the normotensive rat. However, few defects, such as reduced expression of enzymes involved in the metabolism/catabolism of sphingosine-1-phosphate and in the de novo biosynthetic pathways, were exclusively detected in the SHRSP. Although further studies are necessary to fully understand the significance of these findings, they suggest that defects in specific lipid molecules and/or their related metabolic pathways may likely contribute to the pathogenesis of hypertensive target organ damage and may eventually serve as future therapeutic targets to reduce the vascular consequences of hypertension

Treatment with K6PC-5, a selective stimulator of SPHK1, ameliorates intestinal homeostasis in an animal model of Huntington's disease

Abstract Emerging evidence indicates that Huntington's disease (HD) may be described as multi-organ pathology. In this context, we and others have contributed to demonstrate that the disease is characterized by an impairment of the homeostasis of gastro-intestinal (GI) tract. Sphingolipids represent a class of molecules involved in the regulation and maintenance of different tissues and organs including GI system. In this study, we investigated whether the alteration of Sphingosine-1-phosphate (S1P) metabolism, previously described in human HD brains and animal models, is also detectable peripherally in R6/2 HD mice. Our findings indicate, for the first time, that sphingolipid metabolism is perturbed early in the disease in the intestinal tract of HD mice and, its modulation by K6PC-5, a selective activator of S1P synthesis, preserved intestinal integrity and homeostasis. These results further support the evidence that modulation of sphingolipid pathways may represent a potential therapeutic option in HD and suggest that it has also the potential to counteract the peripheral disturbances which may usually complicate the management of the disease and affect patient's quality of life

Características productivas de establecimientos en transición agroecológica y diferencias edáficas con productores convencionales

Se estudiaron sistemas familiares de producción en transición agroecológica (SFTA) y sistemas de producción convencionales (SC), de los partidos de Luján, General Rodríguez y San Andrés de Giles. Se determinó en suelo: materia orgánica, fósforo, pH, CE y respiración; el pH y la conductividad presentaron escasas diferencias entre SFTA y SC, en tanto que la materia orgánica, la respiración y el P fueron superiores en SFTA, indicando que sus sistemas podrían ser sustentables a largo plazo. Se realizaron entrevistas y encuestas a los productores sobre sus formas de organización y comercialización: los SFTA poseen escasas superficies, producen leche de vaca Jersey, cabras y venta de terneros. Los SFTA viven en sus establecimientos, comercializan en ferias locales y vecinos. Presentan formas asociativas, expresan respeto por el ambiente y buscan una mayor calidad de sus productos. Los SC presentan grandes extensiones, no viven en el campo y operan con contratistas.Family production systems in agro-ecological transition (SFTA) and neighbors conventional farm system (SC) matches Lujan, General Rodríguez and San André de Giles were studied. It was determined in soil: organic matter, P, pH, EC and breathing; pH and conductivity showed little difference between SFTA and SC, while organic matter, respiration and P were higher in SFTA, indicating that their systems could be sustainable in the long term. Interviews and surveys were made to farmers on their forms of organization and marketing: the SFTA have poor surfaces, produce milk Jersey cows, goats and selling calves. The SFTA live in their establishments, sold at local fairs and neighbors. They express respect for the environment, shows associative forms and seek a better quality of their products. The SC have large areas, they do not live in the field and operate with contractors.Eje: A1 Sistemas de producción de base agroecológica (Trabajos científicos)Facultad de Ciencias Agrarias y Forestale