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Summary: Salts are essential nutrients required for many physiological processes, and accordingly, their composition and concentration are tightly regulated. Taste is the ultimate sensory modality involved in resource quality assessment, resulting in acceptance or rejection. Here we found that high salt concentrations elicit feeding avoidance in the blood-sucking bug Rhodnius prolixus and elucidate the molecular and neurophysiological mechanisms involved. We found that high-salt avoidance is mediated by a salt-sensitive antennal gustatory receptor neuron (GRN). Using RNAi, we demonstrate that this process requires two amiloride-sensitive pickpocket channels (PPKs; RproPPK014276 and RproPPK28) expressed within these cells. We found that antennal GRNs project to the insect primary olfactory center, the antennal lobes, revealing these centers as potential sites for the integration of taste and olfactory host-derived cues. Moreover, the identification of the gustatory basis of high-salt detection in a hematophagous insect suggests novel targets for the prevention of biting and feeding.

This study aimed to determine the damage mechanisms caused by naturally targeted nanoarchaeosomes made of diether lipids from Halorubrum tebenquichense loaded with curcumin (CUR, nATC), which mediated photodynamic therapy (PDT) on A549 cells and on THP-1-macrophages, two cell types found in airway cancers. The effect of nATC- PDT on vessels modeled with a chicken embryo chorioallantoic membrane (CAM), after dropping the formulations on its surface covered with mucins, was also determined. nATCs are known to efficiently trap CUR for at least six months, constituting easy-to-prepare, stable formulations suitable for nebulization. CUR instead, is easily released from carriers such as liposomes made of ordinary phospholipids and cholesterol after a few weeks. Irradiated at 9 J/cm2, nATC (made of archaeolipids: Tween 80: CUR at 1:0.4:0.04 w:w, size 180 ± 40 nm, ζ potential −24 mV, 150 μg CUR/15 mg lipids/mL) was phototoxic (3.7 ± 0.5 μM IC50), on A549 cells after 24 h. The irradiation reduced mitochondrial membrane potential (ΔΨm), ATP levels and lysosomal functionalism, and caused early apoptotic death and late necrosis of A549 cells upon 24 h. nATC induced higher extra and intracellular reactive oxygen species (ROS) than free CUR. nATC-PDT impaired the migration of A549 cells in a wound healing assay, reduced the expression of CD204 in THP-1 macrophages, and induced the highest levels of IL-6 and IL-8, suggesting a switch of macrophage phenotype from pro-tumoral M2 to antitumoral M1. Moreover, nATC reduced the matrix metalloproteinases (MMP), −2 and −9 secretion, by A549 cells with independence of irradiation. Finally, remarkably, upon irradiation at 9 J/cm2 on the superficial vasculature of a CAM covered with mucins, nATC caused the vessels to collapse after 8 h, with no harm on non-irradiated zones. Overall, these results suggest that nebulized nATC blue light-mediated PDT may be selectively deleterious on superficial tumors submerged under a thick mucin layer.

Para la aprobación, registro y comercialización de medicamentos, agroquímicos, productos de uso doméstico y sustancias cosméticas es necesario estudiar e informar al organismo regulador la potencial toxicidad. Por motivos éticos y económicos, en los últimos años se ha disminuido la utilización de animales de experimentación y se ha fomentado el desarrollo de metodologías alternativas. En el proceso de migración, la OCDE validó procedimientos para evaluar irritación y corrosión ocular y dérmica, mutagenicidad, fototoxicidad, sensibilización y absorción dérmica. Hoy en día es un área en constante investigación y desarrollo ya que aún no se ha logrado reemplazar completamente la calidad de los datos obtenidos en animales. Si bien la tendencia mundial al reemplazo de animales es clara, en Argentina aún no hemos dado el primer paso: no contamos con una ley que regule el uso de animales de experimentación. Las agencias reguladoras (SENASA y ANMAT) continúan solicitando ensayos con animales, pero han manifestado su interés en aceptar evidencia toxicológica obtenida por métodos alternativos. Desde el Laboratorio de Métodos Alternativos al uso de Animales de Experimentación que forma parte de la Plataforma Tecnológica EBAL nos hemos propuesto trabajar en el desarrollo, ejecución, perfeccionamiento y transferencia de metodología alternativa.

RESUMEN: El presente ensayo indaga los cruces, aportes y derivas de las intervenciones artísticas feministas en el arte contemporáneo. Se organiza a partir de una cronología de sus debates iniciales y se pregunta sobre los modos en que se cristalizó en la actualidad, como si de sinónimos se tratara, la idea del arte feminista y arte de mujeres o de género en los diferentes acercamientos a las teorías y metodologías artístico-visuales actuales. En sus preguntas finales, busca indagar en los aportes que desde la geopolítica del sur pueden hacerse a estas intervenciones del archivo feminista artístico para recuperar la politicidad que toda intervención feminista en el arte tiene. ABSTRACT: This paper explores the complex issue of feminist artistic interventions in contemporary art. It traces a genealogy of the debates and main questions around feminist artistic interventions and tries to tackle down the ways in which the notions of feminist art and women’s art have been crystallized as synonyms both by gender theories as well as by visual art’s methodological approaches. Finally, this work highlights the contributions Latin American feminist interventions have made to the art and political fields from a southern geo-political location.

El presente ensayo busca dar cuenta de las relaciones entre el campo de la estética y el de los estudios de género a partir de la articulación de diferentes intervenciones artísticas y los lenguajes multimediales, un debate que sigue siendo crucial para los feminismos del siglo XXI. En primer lugar, se abordará una breve contextualización sobre la relación entre las prácticas artísticas y la crítica a las identidades sexo-genéricas. En segundo lugar, se incluirán algunos de los debates y relaciones entre los usos de algunas plataformas tecnológicas y las intervenciones artistas, así como la relación que tuvo para estas prácticas artísticas feministas em la construccion de sentidos. Luego, se abordan estos temas en el trabajo de dos artistas contemporáneas: Bárbara Kruger y Jenny Holzer quienes utilizan las intervenciones estéticas asociadas a las plataformas tecnológicas para construir imágenes que intervengan los entramados de configuraciones sociales y sexuales del orden simbólico vigente en nuestra cultura, así como algunos de los modos de producción y recepción aún vigentes de la Institución Arte (Burger, 1979). Ambas se caracterizan por sus modos de producción artística y sus intervenciones en grandes capitales urbanas durante los años ’80, fundamentalmente, a partir de la proyección en grandes espacios públicos y la apropiación del lenguaje de los medios de comunicación y el marketing para reconfigurar algunos de sus significados hegemónicos. Por último, no se pretende seguir estrictamente un método que nos conduzca a un análisis semiótico específico de la imagen, o a una semántica de la imagen sino aportar al campo de la comunicación desde um análisis interpetativo y crítico acerca de los modos en que la construcción de conocimiento desde la práctica estética aporta a las Ciencias Sociales y puede generar sentidos que ayuden a discutir la construcción de las significaciones genéricas.

Molecular alterations leading progression of asymptomatic CLL-like high-count monoclonal B lymphocytosis (hiMBL) to chronic lymphocytic leukemia (CLL) remain poorly understood. Recently, genome-wide association studies have found 6p21.3, where the human leukocyte antigen (HLA) system is coded, to be a susceptibility risk region for CLL. Previous studies have produced discrepant results regarding the association between HLA and CLL development and outcome, but no studies have been performed on hiMBL.We evaluated the role of HLA class I (-A, -B and -C) and class II (-DRB1 and -DQB1) in hiMBL/CLL susceptibility, hiMBL progression to CLL, and treatment requirement in a large series of 263 patients diagnosed in our center with hiMBL (n = 156) or Binet A CLL (n = 107).No consistent association between HLA specificities and hiMBL or CLL susceptibility was found. With a median follow-up of 7.7 years, 48/156 hiMBLs (33%) evolved to asymptomatic CLLs, while 16 hiMBLs (10%) and 44 CLLs (41%) required treatment. No HLA specificities were found to be significantly associated with hiMBL progression or treatment in the whole cohort. However, within antigen-experienced immunoglobulin heavy-chain (IGHV)-mutated hiMBLs, which represents the highest proportion of hiMBL cases (81%), the presence of HLA-DQB1*03 showed a trend to a higher risk of progression to CLL (60% vs. 26%, P = 0.062). Moreover, HLA-DQB1*02 specificity was associated with a lesser requirement for 15-year treatment (10% vs. 36%, P = 0.012).In conclusion, our results suggest a role for HLA in IGHV-mutated hiMBL prognosis, and are consistent with the growing evidence of the influence of 6p21 on predisposition to CLL. Larger non-biased series are required to enable definitive conclusions to be drawn.

Resumen El presente ensayo indaga los cruces, aportes y derivas de las intervenciones artísticas feministas en el arte contemporáneo. Se organiza a partir de una cronología de sus debates iniciales y se pregunta sobre los modos en que se cristalizó en la actualidad, como si de sinónimos se tratara, la idea del arte feminista y arte de mujeres o de género en los diferentes acercamientos a las teorías y metodologías artístico-visuales actuales. En sus preguntas finales, busca indagar en los aportes que desde la geopolítica del sur pueden hacerse a estas intervenciones del archivo feminista artístico para recuperar la politicidad que toda intervención feminista en el arte tiene. Palabras clave: Historia del Arte, intervenciones feministas en el arte, arte de mujeres, archivos feministas Abstract This paper explores the complex issue of feminist artistic interventions in contemporary art. It traces a genealogy of the debates and main questions around feminist artistic interventions and tries to tackle down the ways in which the notions of feminist art and women’s art have been crystallized as synonyms both by gender theories as well as by visual art’s methodological approaches. Finally, this work highlights the contributions Latin American feminist interventions have made to the art and political fields from a southern geo-political location. Keywords: History of Art, Feminist interventions in art’s histories, Women’s Art, Feminist Archives.

Cytogenetic studies in clonal plasma cell disorders have mainly been done in whole bone marrow or CD138+ microbead-enriched plasma cells and suggest that recurrent immunoglobulin heavy chain translocations - e.g. t(4;14) -are primary oncogenetic events. The aim of this study was to determine cytogenetic patterns of highly purified aberrant plasma cells (median purity ≥98%) in different clonal plasma cell disorders. We analyzed aberrant plasma cells from 208 patients with multiple myeloma (n=148) and monoclonal gammopathy of undetermined significance (n=60) for the presence of del(13q14), del(17p13) and t(14q32) using multicolor interphase fluorescence in situ hybridization. Additionally, immunoglobulin heavy chain gene arrangements were analyzed and complementarity determining region 3 was sequenced in a subset of patients and combined multicolor interphase fluorescence in situ hybridization/immunofluorescent protein staining analyses were performed in selected cases to confirm clonality and cytogenetic findings. At diagnosis, 96% of cases with multiple myeloma versus 77% of monoclonal gammopathy of undetermined significance cases showed at least one cytogenetic alteration and/or hyperdiploidy. The cytogenetic heterogeneity of individual cases reflected coexistence of cytogenetically-defined aberrant plasma cell clones, and led to the assumption that karyotypic alterations were acquired stepwise. Cases of multiple myeloma and monoclonal gammopathy of undetermined significance frequently showed different but related cytogenetic profiles when other cytogenetic alterations such as deletions/gains of the immunoglobulin heavy chain or the fibroblast growth factor receptor 3 were additionally considered. Interestingly, in 24% of multiple myeloma versus 62% of monoclonal gammopathy of undetermined significance patients with an immunoglobulin heavy chain translocation, aberrant plasma cells with and without t(14q32) coexisted in the same patient. Our data suggest that recurrent immunoglobulin heavy chain translocations might be absent in the primordial plasma cell clone in a significant proportion of patients with clonal plasma cell disorders carrying these cytogenetic alterations.

Myelodysplastic syndromes (MDS) are clonal stem cell disorders which frequently show a hypercellular dysplastic bone marrow (BM) associated with inefficient hematopoiesis and peripheral cytopenias due to increased apoptosis and maturation blockades. Currently, little is known about the role of cell proliferation in compensating for the BM failure syndrome and in determining patient outcome. Here, we analyzed the proliferation index (PI) of different compartments of BM hematopoietic cells in 106 MDS patients compared to both normal/reactive BM (n = 94) and acute myeloid leukemia (AML; n = 30 cases) using multiparameter flow cytometry. Our results show abnormally increased overall BM proliferation profiles in MDS which significantly differ between early/low-risk and advanced/high-risk cases. Early/low-risk patients showed increased proliferation of non-lymphoid CD34(+) precursors, maturing neutrophils and nucleated red blood cells (NRBC), while the PI of these compartments of BM precursors progressively fell below normal values towards AML levels in advanced/high-risk MDS. Decreased proliferation of non-lymphoid CD34(+) and NRBC precursors was significantly associated with adverse disease features, shorter overall survival (OS) and transformation to AML, both in the whole series and when low- and high-risk MDS patients were separately considered, the PI of NRBC emerging as the most powerful independent predictor for OS and progression to AML. In conclusion, assessment of the PI of NRBC, and potentially also of other compartments of BM precursors (e.g.: myeloid CD34(+) HPC), could significantly contribute to a better management of MDS.

The specific genes and genetic pathways associated with pancreatic ductal adenocarcinoma are still largely unknown partially due to the low resolution of the techniques applied so far to their study. Here we used high-density 500 K single nucleotide polymorphism (SNP)-arrays to define those chromosomal regions which most commonly harbour copy number (CN) alterations and loss of heterozygozity (LOH) in a series of 20 PDAC tumors and we correlated the corresponding genetic profiles with the most relevant clinical and histopathological features of the disease. Overall our results showed that primary PDAC frequently display (>70%) extensive gains of chromosomes 1q, 7q, 8q and 20q, together with losses of chromosomes 1p, 9p, 12q, 17p and 18q, such chromosomal regions harboring multiple cancer- and PDAC-associated genes. Interestingly, these alterations clustered into two distinct genetic profiles characterized by gains of the 2q14.2, 3q22.1, 5q32, 10q26.13, 10q26.3, 11q13.1, 11q13.3, 11q13.4, 16q24.1, 16q24.3, 22q13.1, 22q13.31 and 22q13.32 chromosomal regions (group 1; n = 9) versus gains at 1q21.1 and losses of the 1p36.11, 6q25.2, 9p22.1, 9p24.3, 17p13.3 and Xp22.33 chromosomal regions (group 2; n = 11). From the clinical and histopathological point of view, group 1 cases were associated with smaller and well/moderately-differentiated grade I/II PDAC tumors, whereas and group 2 PDAC displayed a larger size and they mainly consisted of poorly-differentiated grade III carcinomas. These findings confirm the cytogenetic complexity and heterozygozity of PDAC and provide evidence for the association between tumor cytogenetics and its histopathological features. In addition, we also show that the altered regions identified harbor multiple cancer associate genes that deserve further investigation to determine their relevance in the pathogenesis of PDAC.