28 research outputs found
Enhanced Transferrin Receptor Expression by Proinflammatory Cytokines in Enterocytes as a Means for Local Delivery of Drugs to Inflamed Gut Mucosa
Therapeutic intervention in inflammatory bowel diseases (IBDs) is often associated with adverse effects related to drug distribution into non-diseased tissues, a situation which attracts a rational design of a targeted treatment confined to the inflamed mucosa. Upon activation of immune cells, transferrin receptor (TfR) expression increases at their surface. Because TfR is expressed in all cell types we hypothesized that its cell surface levels are regulated also in enterocytes. We, therefore, compared TfR expression in healthy and inflamed human colonic mucosa, as well as healthy and inflamed colonic mucosa of the DNBS-induced rat model. TfR expression was elevated in the colonic mucosa of IBD patients in both the basolateral and apical membranes of the enterocytes. Increased TfR expression was also observed in colonocytes of the induced colitis rats. To explore the underlying mechanism CaCo-2 cells were treated with various proinflammatory cytokines, which increased both TfR expression and transferrin cellular uptake in a mechanism that did not involve hyper proliferation. These findings were then exploited for the design of targetable carrier towards inflamed regions of the colon. Anti-TfR antibodies were conjugated to nano-liposomes. As expected, iron-starved Caco-2 cells internalized anti-TfR immunoliposomes better than controls. Ex vivo binding studies to inflamed mucosa showed that the anti-TfR immunoliposomes accumulated significantly better in the mucosa of DNBS-induced rats than the accumulation of non-specific immunoliposomes. It is concluded that targeting mucosal inflammation can be accomplished by nano-liposomes decorated with anti-TfR due to inflammation-dependent, apical, elevated expression of the receptor
Multiancestry analysis of the HLA locus in Alzheimerâs and Parkinsonâs diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinsonâs disease (PD) and Alzheimerâs disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased AÎČ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues
Ecological restoration and productive recovery of saline environments from the Argentine Monte Desert using native plants
The accumulation of soluble salts in soils is one of the main environmental factors that contribute to the loss the productive capacity of ArgentinaÂŽs arid ecosystems. Salinizacion processes, lead to critical states of degradation and desertification. The challenge to recover and improve the productivity of such degraded areas is complex because it should consider restoration strategies that will be integrated with local economic, cultural and social activities. The integrative use and management of different native species in remediation programs is an attractive restoration tool that could improve the productivity capacity of degraded areas. Native species have developed numerous strategies and adaptations that could ensure their survival in saline environments. Nevertheless, species selection, management and appropriate technologies to be used in afforestation programs may be limited because we do not know in detail both the potential and needs of each native species and the environmental characteristics of each site. In this chapter we analyze not only the problem of soil salinization and the challenge of restoring saline environments in Argentina, but also the characteristics of native species of trees, shrubs and grasses of the Monte region, considering their tolerance to saline stress and the provision of goods and services to local populations, which can be useful in restoration programs.Fil: Villagra, Pablo Eugenio. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; ArgentinaFil: Passera, Carlos Bernardo. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Ciencias BiolĂłgicas; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Greco, Silvina Alicia. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Ciencias BiolĂłgicas; ArgentinaFil: Sartor, Carmen Elena. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Ciencias BiolĂłgicas; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Meglioli, Pablo AndrĂ©s. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; ArgentinaFil: Alvarez, Juan Agustin. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales; ArgentinaFil: DĂĄgata, Sofia Leonor. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Ciencias BiolĂłgicas; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Vega Riveros, Cecilia Carolina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales; ArgentinaFil: Alegretti, Andrea VerĂłnica. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Ăridas; ArgentinaFil: Fernandez, Maria Eugenia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Ăridas; ArgentinaFil: Guida Johnson, BĂĄrbara. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Lana, Nerina BelĂ©n. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Cony, Mariano Anibal. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Ăridas; Argentin
Food selection by the guanaco (Lama guanicoe) along an altitudinal gradient in the Southern Andean Precordillera (Argentina)
Wild ungulates like the guanaco are exposed to important changes in climate and plant diversity along altitudinal gradients in the Andes Mountains, such as in the Southern Andean Precordillera where three phytogeographic provinces are present in altitudinal belts. The guanacoâs diet and food availability were seasonally analyzed using microhistological analysis and point-quadrat transects at six sampling sites, representative of the phytogeographic belts along the altitudinal gradient. Plant cover and diversity decreased with growing altitude. Richness of plant species was poorer at the summit than in the lower altitudes, whereas the proportion of species eaten by guanacos increased with altitude. The diet included 77 species. Grasses were preferred and shrubs were avoided all year round. The grass Poa spp. occupied more than 50 % of the diet at all altitudes. Grasses were the main dietary item even at low altitudes, where shrubs constituted the main food available. Decreasing generalism with descending phytogeographic belts agrees with the prediction for altitudinal gradients. The increase of diversity in the diet during the winter decline of plant cover at high and middle altitudes follows that expected from the optimal foraging theory. The winter decline of vegetation and the dietary shift from grazing to browsing proved to be stronger as altitude increases and the climate become more rigorous. Plant species richness, food scarcity, and climate severity are relevant variables to explain altitudinal and seasonal changes in the diet of adaptive ungulates in mountain environments, such as the guanaco in the Southern Andean Precordillera.Fil: Puig, Silvia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Ăridas; ArgentinaFil: Rosi, Maria Irene. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Ăridas; ArgentinaFil: Videla, Fernando. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Ăridas; ArgentinaFil: Mendez, Eduardo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Ăridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Ăridas; Argentin