Histamine H4 receptor agonists induce epithelial-mesenchymal transition events and enhance mammosphere formation via Src and TGF-β signaling in breast cancer cells

Epithelial-mesenchymal transition (EMT) contributes to cell invasion and metastasis during the progression of epithelial cancers. Though preclinical evidence suggests a role for histamine H4 receptor (H4R) in breast cancer growth, its function in the EMT is less known. In this study we proposed to investigate the effects of H4R ligands on EMT and mammosphere formation as a surrogate assay for cancer stem cells in breast cancer cells with different invasive phenotype. We also investigated the participation of Src and TGF-β signaling in these events. Breast cancer cells were treated with the H4R agonists Clobenpropit, VUF8430 and JNJ28610244 and the H4R antagonist JNJ7777120. Immunodetection studies showed cytoplasmic E-cadherin, cytoplasmic and nuclear beta-catenin, nuclear Slug and an increase in vimentin and α-smooth muscle actin expression. There was also an enhancement in cell migration and invasion assessed by transwell units. All these effects were prevented by JNJ7777120. Moreover, H4R agonists induced an increase in phospho-Src levels detected by Western blot. Results revealed the involvement of phospho-Src in EMT events. Upon treatment with H4R agonists there was an increase in phospho-ERK1/2 and TGF-β1 levels by Western blot, in Smad2/3 positive nuclei by indirect immunofluorescence, and in tumor spheres formation by the mammosphere assay. Notably, the selective TGF-β1 kinase/activin receptor-like kinase inhibitor A83-01 blocked these effects. Moreover, cells derived from mammospheres exhibited higher Slug expression and enhanced migratory behavior. Collectively, findings support the interaction between H4R and TGF-β receptor signaling in the enhancement of EMT features and mammosphere formation and point out intracellular TGF-β1 as a potential mediator of these events.Fil: Galarza, Tamara Ester. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Táquez Delgado, Mónica Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mohamad, Nora A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Martin, Gabriela Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Cricco, Graciela P.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Granulomatous-like immune reaction and hepatic fibrosis induced by Schistosoma haematobium immature worms

Golden hamsters were inoculated with Schistosoma haematobium cercariae to examine histological lesions at different time points over an 18 month period of infection. Hamsters were sacrificed 26 weeks and 82 weeks after inoculation. The parasite was found in the blood and in the liver of infected animals as was expected, but we found exclusively male worms, no female worms nor eggs. Interestingly we observed unexpected hepatic lesions induced by S. haematobium immature male worms alone in the golden hamster, characteristic of schistosome eggs. Samples from liver, kidneys, lungs, bladder and gastrointestinal tract were collected during necropsy to evaluate injuries induced by S. haematobium. Notably we observed hepatitis in the liver of infected hamsters, no lesions were found in other organs. We also found liver fibrosis in infected hamsters. This study provides further experimental evidence for the role that schistosome worms, and their derived antigens, may play in the pathology of the infection and modulation of liver chronic inflammation in the murine model of schistosomiasis

Dry Matter and Macronutrient Content of Green Fertilisers Incorporated in two Andisol Soils, Municipality of Pasto – Colombia

En la zona alto andina el continuo cambio en el uso de cobertura, viene evidenciando efetos en la calidad del suelo, por tanto loa abonos verdes se presentan como una alternativa amigable con el ambiente. Con lo anterior, El objetivo de esta investigación fue determinar el contenido de materia seca y macronutrientes en siete abonos verdes (AV) y comparar su aplicación en dos suelos andisoles. Mediante un diseño experimental de Bloques Completos al Azar (BCA) con tres repeticiones y ocho tratamientos: Vicia sativa, Plantago lanceolata, Medicago sativa, Trifolium repens, Alnus jorullensis, Lupinus mutabilis y Brassica napus. Se implementó los AV y se tomo muestras a los 60 dias, en laboratorio se determinó las variables V1: Materia Seca, V2: contenido de humedad, V3: Contenido de N, V4: P y V5: K. Se evidneció algunas diferencias significativas entre AV y variables; pero no entre localidades, lo que sugiere una gran adaptación de las especies evaluadas a los tipos de suelo.In the high Andean area the continuous change in the use of cover, has been evidencing efficiencies in the quality of the soil, therefore the green fertilizers are presented as an environmentally friendly alternative. With the above, the objective of this research was to determine the content of dry matter and macronutrients in seven green fertilizers (GF) and compare their application in two andisol soils. Through an experimental design of Random Complete Blocks (BCR) with three repetitions and eight treatments: Vicia sativa, Plantago lanceolata, Medicago sativa, Trifolium repens, Alnus jorullensis, Lupinus mutabilis and Brassica napus. The GF was implemented and samples were taken at 60 days, in laboratory the variables V1 were determined: Dry Matter, V2: moisture content, V3: N content, V4: P and V5: K. Some significant differences between GF and variables were evident; but not between localities, which suggests a great adaptation of the species evaluated to soil types

Hazardous faults of South America; compilation and overview

The heterogeneous South American geology has coined a wide variety of neotectonic settings where crustal seismogenic sources do occur. This fact has led to different approaches for mapping and inventory neotectonic structures. The South American Risk Assessment project promoted the discussion and update under uniform standards of the available information on neotectonic deformation, for its application in regional Probabilistic Seismic Hazard Assessments. As a result, 1533 hazardous faults have been inventoried onshore South America, 497 of them qualifying to feed the engine model driving probabilistic maps. Main hazardous structures are concentrated throughout the eastern boundary of the Northern Andean Sliver and along the foreland-facing Andean Thrust Front. Space geodesy and seismicity illuminate the seismogenic significance of these deformation belts, although few neotectonic surveys have been conducted to date in the latter region. The characteristics of the main structures or deformation zones are here outlined according to their filiation to neotectonic domains, which are dependant on the geologic, seismotectonic, or morphotectonic settings in Andean and extra-Andean regions. The knowledge accrued on the hazardous faults in South America here compiled, reinforces the fact that some of these structures constitute significant hazard sources for many urban areas and critical facilities and should be incorporated in seismic hazard assessments. However, the available fault data are insufficient in many cases or carry significant epistemic uncertainties for fault source characterization. This contribution aims to summarize the present knowledge on the South American hazardous faults as well as the main challenges for successful fault data incorporation into seismic hazard models

Myeloid-Derived Suppressor Cells Show Different Frequencies in Diabetics and Subjects with Arterial Hypertension

Type 2 diabetes mellitus (DM2) is strongly associated with other comorbidities such as obesity, atherosclerosis, and hypertension. Obesity is associated with sustained low-grade inflammatory response due to the production of proinflammatory cytokines. This inflammatory process promotes the differentiation of some myeloid cells, including myeloid-derived suppressor cells (MDSCs). In this study, two groups of individuals were included: DM2 patients and non-DM2 individuals with similar characteristics. Immunolabeling of CD15+ CD14- and CD33+ HLA-DR-/low was performed from whole peripheral blood, and samples were analyzed by flow cytometry, and frequencies of MDSCs and the relationship of these with clinical variables, cytokine profile (measured by cytometric bead array), and anthropometric variables were analyzed. The frequency of CD33+ HLA-DR-/low MDSCs (that produce IL-10 and TGF-β, according to an intracellular detection) is higher in patients with DM2 (P < 0:05), and there is a positive correlation between the frequency of CD15+ CD14- and CD33+ HLA-DR-/low MDSC phenotypes. DM2 patients have an increased concentration of serum IL-5 (P < 0:05). Also, a negative correlation between the frequency of CD15+CD14- MDSCs and LDL cholesterol was found. Our group of DM2 patients have an increased frequency of mononuclear MDSC CD33+ HLA-DR-/low that produce TGF-β and IL-10. These cytokines have been associated with immune modulation and reduced T cell responses. DM2 and non-DM2 subjects show a similar cytokine profile, but the DM2 patients have anincreased concentration of IL-5

VE-Cadherin modulates ß-catenin/TCF-4 to enhance Vasculogenic Mimicry

Vasculogenic Mimicry (VM) refers to the capacity to form a blood network from aggressive cancer cells in an independent way of endothelial cells, to provide nutrients and oxygen leading to enhanced microenvironment complexity and treatment failure. In a previous study, we demonstrated that VE-Cadherin and its phosphorylation at Y658 modulated kaiso-dependent gene expression (CCND1 and Wnt 11) through a pathway involving Focal Adhesion kinase (FAK). In the present research, using a proteomic approach, we have found that ß-catenin/TCF-4 is associated with nuclear VE-cadherin and enhances the capacity of malignant melanoma cells to undergo VM in cooperation with VE-Cadherin; in addition, preventing the phosphorylation of Y658 of VEcadherin upon FAK disabling resulted in VE-Cadherin/ß-catenin complex dissociation, increased ß-catenin degradation while reducing TCF-4-dependent genes transcription (C-Myc and Twist-1). Uveal melanoma cells knockout for VE-Cadherin loses ß-catenin expression while the rescue of VE-Cadherin (but not of the phosphorylation defective VE-Cadherin Y658F mutant) permits stabilization of ß-catenin and tumor growth reduction in vivo experiments. In vivo, the concomitant treatment with the FAK inhibitor PF-271 and the anti-angiogenic agent bevacizumab leads to a strong reduction in tumor growth concerning the single treatment. In conclusion, the anomalous expression of VE-Cadherin in metastatic melanoma cells (from both uveal and cutaneous origins), together with its permanent phosphorylation at Y658, favors the induction of the aggressive VM phenotype through the cooperation of ß-catenin with VE-Cadherin and by enhancing TCF-4 genes-dependent transcription.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness SAF2015-70520-R, the Spanish Ministry of Science and Technology RTI2018-098968-B-I00, CIBERONC ISCIII CB16/12/00421 and Junta de Andalucía, a project of Excellence from Junta de Andalucía P10-CTS-0662, P12-CTS-383 to FJO. Fundación Domingo Martínez to FJO. Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (PAIDI 2020, POSTDOC_21_00865) to DD-B. Fundación Getthi ONC18PE01/2022 to DAE, AT

Cien días vistos por CINEP (No. 79 jul-ago 2013)

El país que no pasa por La Habana. La edición no. 79 de la revista Cien días vistos por CINEP/PPP presenta varios artículos elaborados por el equipo de investigadores y educadores del Centro, donde analizan e invitan a reflexionar acerca del valor y el sentido del diálogo en la construcción de la paz, entendida como cese del conflicto armado y a la vez como proceso de construcción social, política, económica y cultural. Igualmente una paz comprendida como tarea del Estado y de la sociedad en su conjunto. Para esto los artículos plantean preguntas que analizan ¿cómo puede la sociedad civil aportar a un escenario de posconflicto? y ¿cómo la institucionalidad pública y social debe procurar con todos sus recursos, los procesos de reconciliación, de perdón, de búsqueda de la verdad, de no repetición y reconstitución de los tejidos sociales?Índice: Paz. "Posconflicto y política agraria. Una mirada a la experiencias internacionales" por Sergio Coronado y Zohanny Arboleda; "Repensar el diálogo: Una lectura complementaria del papel de la sociedad civil en el proceso de paz" por Diana Chavarro y David Rampf; "Las posibilidades regionales de la paz" por Víctor Barrera. Movimientos sociales. "Protestas en el Catatumbo: ¿y la historia?" por Ana María Restrepo; "Cartas van, cartas vienen" por Mauricio Archila. Derechos Humanos. "Ampliación al fuero penal militar: entre fueros y desafueros" por Mónica Osorio Aguiar. Economía."Para una etapa posnegación Colombia necesita invertir seriamente en condiciones de tipo estructural": Cesar Vallejo por Mónica Osorio Aguiar. Especial. Pronunciamiento de CINEP/Programa por la Paz sobre el Marco Jurídico para la Paz ante la Corte Constitucional por Alejandro Angulo Novoa, S.J

Rescatando películas: directores malos, desconocidos o one hit wonders

¿Michael Bay y Robert Rodríguez realmente tienen alguna película rescatable? ¿Se acuerdan de cintas de Herk Harvey, Les Blank o Jonathan Glazer? Pues bien, a continuación, una lista comentada de películas muy apreciables de directores malos o casi olvidados para algunos de nuestros colaboradores

Preliminary assessment of the knowledge gaps to improve nature conservation of soil biodiversity

20 páginas.- 2 tablas.- referencias.-In the past decades, there has been an increasing awareness of the importance of Nature Conservation of Soil Biodiversity. Approximately 59% of all biodiversity on the planet is comprised of soil living organisms (Anthony et al. 2023), ranging from microorganisms to vertebrate species (FAO et al. 2020, Anthony et al. 2023). Soil biodiversity plays a central role in soil health and ecosystem services, as the activities of soil biota support the delivery of various ecosystem services, such as carbon sequestration, nutrient cycling, prevention of soil erosion, pest control, and cleaning of air and water (Banerjee and van der Heijden 2023, Creamer et al. 2022, Pulleman et al. 2012). However, soil biodiversity is currently threatened by intensive agriculture and forestry as well as soil sealing in urban environments. Protecting soil biodiversity and thus its ecosystem functions and services will have positive effects on a number of sustainability development goals (SDGs), including water quality and food security, among others (FAO et al. 2020, Köninger et al. 2022). Nevertheless, recent work did not find positive effects of current conservation practices on soil biodiversity and its ecosystem functions (Zeiss et al. 2022). The authors suggest this is predominantly because the priorities and the decision-making paradigms used for selection of sites for conservation do not take into account soil biodiversity, its associated ecosystem functions, or the value of belowground ecosystems to human well-being and economic development (Bardgett and van der Putten 2014, FAO et al. 2020, Zeiss et al. 2022). While biodiversity-friendly management approaches, such as ecological intensification (Kleijn et al. 2019), regenerative agriculture and agroecology (Barrios et al. 2023, FAO 2023, Grilli et al. 2023) are receiving increasing attention, studies focused on conservation of soil biodiversity and its ecosystem functions are still limited (Bardgett and van der Putten 2014, FAO et al. 2020, Zeiss et al. 2022). Thus, there is a stark need for identifying knowledge gaps and new research and innovation to help protect and conserve soil biodiversity, the ecosystem services they provide, and their impact on human health and economics.Peer reviewe