Hierarchical and selective roles of galectins in hepatocarcinogenesis, liver fibrosis and inflammation of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents a global health problem. Infections with hepatitis B or C virus, non-alcoholic steatohepatitis disease, alcohol abuse, or dietary exposure to aflatoxin are the major risk factors to the development of this tumor. Regardless of the carcinogenic insult, HCC usually develops in a context of cirrhosis due to chronic inflammation and advanced fibrosis. Galectins are a family of evolutionarily-conserved proteins defined by at least one carbohydrate recognition domain with affinity for β-galactosides and conserved sequence motifs. Here, we summarize the current literature implicating galectins in the pathogenesis of HCC. Expression of ?proto-type? galectin-1, ?chimera- type? galectin-3 and ?tandem repeat-type? galectin- 4 is up-regulated in HCC cells compared to their normal counterparts. On the other hand, the ?tandemrepeat- type? lectins galectin-8 and galectin-9 are downregulated in tumor hepatocytes. The abnormal expression of these galectins correlates with tumor growth, HCC cell migration and invasion, tumor aggressiveness, metastasis, postoperative recurrence and poor prognosis. Moreover, these galectins have important roles in other pathological conditions of the liver, where chronic inflammation and/or fibrosis take place. Galectin-based therapies have been proposed to attenuate liver pathologies. Further functional studies are required to delineate the precise molecular mechanisms through which galectins contribute to HCC.Fil: Bacigalupo, Maria Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas; Argentina;Fil: Manzi, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas; Argentina;Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biologia y Medicina Experimental (i); Argentina;Fil: Troncoso, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas; Argentina

Coupled Mass-Spectrometry-Based Lipidomics Machine Learning Approach for Early Detection of Clear Cell Renal Cell Carcinoma

A discovery-based lipid profiling study of serum samples from a cohort that included patients with clear cell renal cell carcinoma (ccRCC) stages I, II, III, and IV (n = 112) and controls (n = 52) was performed using ultraperformance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry and machine learning techniques. Multivariate models based on support vector machines and the LASSO variable selection method yielded two discriminant lipid panels for ccRCC detection and early diagnosis. A 16-lipid panel allowed discriminating ccRCC patients from controls with 95.7% accuracy in a training set under cross-validation and 77.1% accuracy in an independent test set. A second model trained to discriminate early (I and II) from late (III and IV) stage ccRCC yielded a panel of 26 compounds that classified stage I patients from an independent test set with 82.1% accuracy. Thirteen species, including cholic acid, undecylenic acid, lauric acid, LPC(16:0/0:0), and PC(18:2/18:2), identified with level 1 exhibited significantly lower levels in samples from ccRCC patients compared to controls. Moreover, 3α-hydroxy-5α-androstan-17-one 3-sulfate, cis-5-dodecenoic acid, arachidonic acid, cis-13-docosenoic acid, PI(16:0/18:1), PC(16:0/18:2), and PC(O-16:0/20:4) contributed to discriminate early from late ccRCC stage patients. The results are auspicious for early ccRCC diagnosis after validation of the panels in larger and different cohorts.Fil: Manzi, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Palazzo, Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Knott, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Beauseroy, Pierre. Université de Technologie de Troyes; FranciaFil: Yankilevich, Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Giménez, María Isabel. Hospital Italiano; ArgentinaFil: Monge, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentin

Metabolic Footprinting of a Clear Cell Renal Cell Carcinoma in Vitro Model for Human Kidney Cancer Detection

A protocol for harvesting and extracting extracellular metabolites from an in vitro model of human renal cell lines was developed to profile the exometabolome by means of a discovery-based metabolomics approach using ultraperformance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry. Metabolic footprints provided by conditioned media (CM) samples (n = 66) of two clear cell Renal Cell Carcinoma (ccRCC) cell lines with different genetic backgrounds and a nontumor renal cell line, were compared with the human serum metabolic profile of a pilot cohort (n = 10) comprised of stage IV ccRCC patients and healthy individuals. Using a cross-validated orthogonal projection to latent structures-discriminant analysis model, a panel of 21 discriminant features selected by iterative multivariate classification, allowed differentiating control from tumor cell lines with 100% specificity, sensitivity, and accuracy. Isoleucine/leucine, phenylalanine, N-lactoyl-leucine, and N-acetyl-phenylalanine, and cysteinegluthatione disulfide (CYSSG) were identified by chemical standards, and hydroxyprolyl-valine was identified with MS and MS/MS experiments. A subset of 9 discriminant features, including the identified metabolites except for CYSSG, produced a fingerprint of classification value that enabled discerning ccRCC patients from healthy individuals. To our knowledge, this is the first time that N-lactoyl-leucine is associated with ccRCC. Results from this study provide a proof of concept that CM can be used as a serum proxy to obtain disease-related metabolic signatures.Fil: Knott, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Manzi, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Zabalegui, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Salazar, Mario Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; ArgentinaFil: Puricelli, Lydia Ines. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monge, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentin

Epigrafía del Paisaje en el análisis de la materialidad funeraria

In this paper, we propose to study the funerary dimension through iconographic representations and descriptions about the provision of offerings in relation to political institutions (temples and palaces) and the state administration of Ur in Mesopotamia and Thebes in Egypt, considering the places in the landscape, valuing both its physical properties and weighing its intangible aspects. To this end, we focus on an approach that is based on the analysis of documents that refer to funeral spaces, but also highlighting aspects concerning their production, distribution, and storage. In this way, elements related to their systemic contexts and their semantic characters (or internal components) are emphasized. For this reason, we call this analysis perspective Landscape Epigraphy and it can be thought of in parallel to that of «materiality of the linguistic sign», which maintains that writing can be considered a materiality that recreates the universe of social relations, by bring together in the modality of texts and iconographies, cultural interventions, and mental representations with the selected places in the regional space. To do this, a tripartition of the landscape between humans, places, and objects is contemplated, focusing on: (a) practices, (b) agents, and (c) spatialities.En el presente trabajo, proponemos estudiar la dimensión funeraria a través de representaciones iconográficas y descripciones sobre la provisión de ofrendas en relación con las instituciones políticas (templos y palacios) y la administración estatal de Ur en Mesopotamia y de Tebas en Egipto, considerando los lugares en el paisaje, valorando tanto sus propiedades físicas como ponderando sus aspectos intangibles. A tal fin, nos focalizamos en un abordaje que se sustenta en el análisis de documentos que refieren a espacios funerarios, pero destacando también aspectos concernientes a su producción, distribución y almacenamiento. De este modo, enfatizamos elementos relativos a sus contextos sistémicos y sus caracteres semánticos (o componentes internos). Por tal motivo, a esta perspectiva de análisis, la denominamos Epigrafía del Paisaje y puede ser pensada en paralelo a la de «materialidad del signo lingüístico», la cual sostiene que la escritura puede considerarse una materialidad que recrea el universo de las relaciones sociales, al reunir en la modalidad de textos e iconografías, intervenciones culturales y representaciones mentales con los lugares seleccionados en el espacio regional. Para ello, se contempla una tripartición del paisaje entre humanos, lugares y objetos haciendo foco en: (a) las prácticas, (b) los agentes intervinientes y (c) las espacialidades reconocibles

The Theban Tomb 49 and its owner, in the sacred landscape of west Thebes, Egypt

La tumba de Neferhotep (TT49) es un monumento privado, cuya localización habría tenido vinculaciones con las fisonomías naturales y la dotación material del paisaje, en la realización de prácticas funerarias del Reino Nuevo. La escasa conservación de la evidencia material requirió de la implementación de vías analíticas que tras-cendieran los enfoques egiptológicos tradicionales privilegiando el estudio del comportamiento humano. La exis-tencia de registros documentales y arqueológicos hizo evidente la necesidad de plantear investigaciones interdisci-plinarias, puesto que tanto la localización de la tumba en el paisaje como su construcción y decoración atendieron tanto a cuestiones prácticas -depositación de momias y equipamiento funerario-, como simbólicas -ritos mor-tuorios- y sociales -alianzas-. Los lineamientos teóricos interrelacionan conceptos provenientes de la arqueología, enfatizando la dotación arquitectónica y simbólica del espacio y las propiedades físicas del registro material en la conformación de depósitos; de la historia, en cuanto a la reproducción social y construcción de memoria cultural; y de la antropología, para la comprensión del equilibrio social y trascendental a los que contribuyeron las prácticas rituales. Su aplicación intenta reconocer cómo opera la construcción de memoria cultural en la consolidación de un paisaje sacralizado, sensible a cambios ideológicos y ‘dinamizados’ a través de las celebraciones rituales.The starting point is the study of Neferhotep’s tomb (TT49) and its links to the natural physiognomy and material endowment of the regional landscape for the realization of the New Kingdom funerary practices. The poor preservation of the material evidence required to implement analytical ways that transcend traditional Egyptological approaches -monumentalists and classifiers, and privilege the study of human behavior. The exis-tence of documentary and archaeological records made evident the need to establish interdisciplinary researches, inasmuch their location in the landscape, its construction and decoration attended practical issues –deposition of mummies- as symbolic -funerary rites-, and social - alliances-. Consequently, theoretical guidelines interrelate concepts coming from: archaeology, emphasizing the symbolic allocation of the space and the physical properties of the material record in the formation of deposits; history, in terms of social reproduction and construction of cultural memory; and anthropology, for understanding the social and transcendental balance for which the ritual practices have contributed. It is expected to recognize how cultural memory building operates in the consolida-tion of a sacred landscape, sensitive to ideological changes and ‘invigorated’ by ritual celebrations

Effects of Ultrasound Irradiation on the Synthesis of Metal Oxide Nanostructures

High intensity ultrasound can be used for the production of novel nanomaterials, including metal oxides. According to previous works in this field, the most notable effects are consequence of acoustic cavitation. In this context, we have studied the preparation of different materials in the presence of ultrasound, including N-doped TiO2 nanopowder, NiTiO3 nanorods and MnOx thin films. Ultrasound did not show a significant effect in all the cases. Exclusively for NiTiO3 nanorods a reduction of the final particle size occurs upon ultrasonic irradiation. From these results, it can be concluded that the ultrasound irradiation does not always play a key role during the synthesis of metal oxides. The effects seem to be particularly relevant in those cases where mass transport is highly hindered and in those procedures that require the rupture of nanoparticle aggregates to obtain a homogenous dispersion.We want to acknowledge the Spanish Ministry of Economy and Competitiveness (MINECO) for financial support through projects PRI-PIBIN-2011-0816 and MAT2012-37676 (FONDOS FEDER). V. Manzi-Orezzoli is grateful to the Universitat d’Alacant for the award of a research initiation grant

Aportes para la enseñanza de la escritura

Se organiza en cinco secciones. La primera presenta el enfoque de la enseñanza de la escritura en la región, a partir de la revisión del análisis curricular que sirve como marco de evaluación de las pruebas, especificando los propósitos, objetivos, características y orientación de la enseñanza de esta disciplina. La segunda describe la prueba TERCE, relevando los aprendizajes que evalúa a partir de las dimensiones e indicadores que componen las rúbricas con que se corrigieron los textos producidos por los estudiantes. La tercera sección analiza los resultados de los estudiantes en los indicadores evaluados en las pruebas de tercer y sexto grados. En la cuarta sección se muestran ejemplos de respuestas que representan distintos niveles de logro y, en la quinta, se entregan sugerencias o propuestas de prácticas pedagógicas para promover que los estudiantes alcancen los niveles más avanzados

Nefrectomía totalmente laparoscópica para donante vivo de riñón: características y desenlaces en una institución de alta complejidad en Colombia. Serie de casos

Introducción. El trasplante es la mejor opción de tratamiento para los pacientes con enfermedad renal terminal, sin embargo, existe discrepancia entre las listas de espera y la disponibilidad de órganos a partir de la donación cadavérica. Buscando aumentar el número de órganos disponibles se implementó el trasplante con donante vivo. A partir de la introducción de técnicas mínimamente invasivas para la nefrectomía, el donante vivo ha logrado cifras cercanas al 50 % de los trasplantes realizados en muchas instituciones, debido a los beneficios propios del procedimiento. El objetivo de este estudio fue describir los resultados después de la incorporación del procedimiento totalmente laparoscópico en nuestra institución. Métodos. Se hizo un análisis retrospectivo de las características de los pacientes llevados a nefrectomía para obtención de injerto por técnica totalmente laparoscópica y los resultados en un solo centro en Cali, Colombia, desde noviembre de 2019 hasta octubre de 2022. Los datos fueron obtenidos mediante la revisión de las historias clínicas electrónicas. Resultados. Se realizaron 78 nefrectomías para obtención de injerto con técnica totalmente laparoscópica. El tiempo operatorio promedio fue de 152 minutos, el sangrado promedio fue de 12 ml, la estancia hospitalaria promedio del donante fue de 2,8 días. La tasa de complicaciones fue de 7,6 % (4 pacientes con complicación Clavien-Dindo I y 2 pacientes Clavien-Dindo IIIb). No se presentó ningún caso de mortalidad. Conclusiones. La técnica totalmente laparoscópica resulta ser una técnica segura con baja tasa de morbilidad y excelentes beneficios para los donantes

Marine organic matter in the remote environment of the Cape Verde islands-an introduction and overview to the MarParCloud campaign

The project MarParCloud (Marine biological production, organic aerosol Particles and marine Clouds: a process chain) aims to improve our understanding of the genesis, modification and impact of marine organic matter (OM) from its biological production, to its export to marine aerosol particles and, finally, to its ability to act as ice-nucleating particles (INPs) and cloud condensation nuclei (CCN). A field campaign at the Cape Verde Atmospheric Observatory (CVAO) in the tropics in September-October 2017 formed the core of this project that was jointly performed with the project MARSU (MARine atmospheric Science Unravelled). A suite of chemical, physical, biological and meteorological techniques was applied, and comprehensive measurements of bulk water, the sea surface microlayer (SML), cloud water and ambient aerosol particles collected at a ground-based and a mountain station took place. Key variables comprised the chemical characterization of the atmospherically relevant OM components in the ocean and the atmosphere as well as measurements of INPs and CCN. Moreover, bacterial cell counts, mercury species and trace gases were analyzed. To interpret the results, the measurements were accompanied by various auxiliary parameters such as air mass back-trajectory analysis, vertical atmospheric profile analysis, cloud observations and pigment measurements in seawater. Additional modeling studies supported the experimental analysis. During the campaign, the CVAO exhibited marine air masses with low and partly moderate dust influences. The marine boundary layer was well mixed as indicated by an almost uniform particle number size distribution within the boundary layer. Lipid biomarkers were present in the aerosol particles in typical concentrations of marine background conditions. Accumulation-and coarse-mode particles served as CCN and were efficiently transferred to the cloud water. The ascent of ocean-derived compounds, such as sea salt and sugar-like compounds, to the cloud level, as derived from chemical analysis and atmospheric transfer modeling results, denotes an influence of marine emissions on cloud formation. Organic nitrogen compounds (free amino acids) were enriched by several orders of magnitude in submicron aerosol particles and in cloud water compared to seawater. However, INP measurements also indicated a significant contribution of other non-marine sources to the local INP concentration, as (biologically active) INPs were mainly present in supermicron aerosol particles that are not suggested to undergo strong enrichment during ocean-atmosphere transfer. In addition, the number of CCN at the supersaturation of 0.30 % was about 2.5 times higher during dust periods compared to marine periods. Lipids, sugar-like compounds, UV-absorbing (UV: ultraviolet) humic-like substances and low-molecularweight neutral components were important organic compounds in the seawater, and highly surface-active lipids were enriched within the SML. The selective enrichment of specific organic compounds in the SML needs to be studied in further detail and implemented in an OM source function for emission modeling to better understand transfer patterns, the mechanisms of marine OM transformation in the atmosphere and the role of additional sources. In summary, when looking at particulate mass, we see oceanic compounds transferred to the atmospheric aerosol and to the cloud level, while from a perspective of particle number concentrations, sea spray aerosol (i.e., primary marine aerosol) contributions to both CCN and INPs are rather limited. © Author(s) 2020

Marine organic matter in the remote environment of the Cape Verde islands – an introduction and overview to the MarParCloud campaign

The project MarParCloud (Marine biological production, organic aerosol Particles and marine Clouds: a process chain) aims to improve our understanding of the genesis, modification and impact of marine organic matter (OM) from its biological production, to its export to marine aerosol particles and, finally, to its ability to act as ice-nucleating particles (INPs) and cloud condensation nuclei (CCN). A field campaign at the Cape Verde Atmospheric Observatory (CVAO) in the tropics in September–October 2017 formed the core of this project that was jointly performed with the project MARSU (MARine atmospheric Science Unravelled). A suite of chemical, physical, biological and meteorological techniques was applied, and comprehensive measurements of bulk water, the sea surface microlayer (SML), cloud water and ambient aerosol particles collected at a ground-based and a mountain station took place. Key variables comprised the chemical characterization of the atmospherically relevant OM components in the ocean and the atmosphere as well as measurements of INPs and CCN. Moreover, bacterial cell counts, mercury species and trace gases were analyzed. To interpret the results, the measurements were accompanied by various auxiliary parameters such as air mass back-trajectory analysis, vertical atmospheric profile analysis, cloud observations and pigment measurements in seawater. Additional modeling studies supported the experimental analysis. During the campaign, the CVAO exhibited marine air masses with low and partly moderate dust influences. The marine boundary layer was well mixed as indicated by an almost uniform particle number size distribution within the boundary layer. Lipid biomarkers were present in the aerosol particles in typical concentrations of marine background conditions. Accumulation- and coarse-mode particles served as CCN and were efficiently transferred to the cloud water. The ascent of ocean-derived compounds, such as sea salt and sugar-like compounds, to the cloud level, as derived from chemical analysis and atmospheric transfer modeling results, denotes an influence of marine emissions on cloud formation. Organic nitrogen compounds (free amino acids) were enriched by several orders of magnitude in submicron aerosol particles and in cloud water compared to seawater. However, INP measurements also indicated a significant contribution of other non-marine sources to the local INP concentration, as (biologically active) INPs were mainly present in supermicron aerosol particles that are not suggested to undergo strong enrichment during ocean–atmosphere transfer. In addition, the number of CCN at the supersaturation of 0.30 % was about 2.5 times higher during dust periods compared to marine periods. Lipids, sugar-like compounds, UV-absorbing (UV: ultraviolet) humic-like substances and low-molecular-weight neutral components were important organic compounds in the seawater, and highly surface-active lipids were enriched within the SML. The selective enrichment of specific organic compounds in the SML needs to be studied in further detail and implemented in an OM source function for emission modeling to better understand transfer patterns, the mechanisms of marine OM transformation in the atmosphere and the role of additional sources. In summary, when looking at particulate mass, we see oceanic compounds transferred to the atmospheric aerosol and to the cloud level, while from a perspective of particle number concentrations, sea spray aerosol (i.e., primary marine aerosol) contributions to both CCN and INPs are rather limited