Propuesta de lineamientos estratégicos orientados a intensificar la cobertura actual de mercado de una empresa sustentada en economía circular

Trabajo final (Licenciatura en Administración con orientación en Dirección General y Comercialización)Propósito: Brindar una propuesta de lineamientos estratégicos a la empresa sustentada en los principios de la Economía Circular orientados a intensificar la cobertura actual de mercado en el barrio de Nueva Córdoba, ya que en dicha zona se recolecta una proporción de bolsas que duplica el volumen total proveniente de zona norte. Metodología: Se desarrollaron entrevistas semiestructuradas tanto a socios como a empleados de la empresa, seguido por cuestionarios destinados a los responsables de los puntos de recolección y a los consumidores. Se identificaron los factores claves de éxito del sector, se realizó un mapa de posiciones competitivas y además un análisis descriptivo de los consumidores con el propósito de identificar los segmentos objetivos. Por último, se propuso lineamientos estratégicos en conjunto con un cuadro de mando integral e indicadores como mecanismo de control y evaluación. Conclusiones: Finalmente se arribó al resultado de que es de vital importancia determinar un marco estratégico sólido para el logro del objetivo de intensificar su cobertura actual de mercado en el barrio de Nueva Córdoba. A tal fin se identificaron los factores claves de éxito de la industria, el posicionamiento competitivo de la empresa y los segmentos objetivos de mercado para impulsar el crecimiento, el volumen procesado y, por lo tanto, la rentabilidad de la organización. Limitaciones: Es posible destacar la resistencia en los miembros de la organización a compartir información relevante, además la muestra tomada puede ignorar algún atributo clave y, por último, los riesgos a posibles sesgos en la información relevada.Fil: Astrada, Irina Trinidad. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Bassi, Camila Soledad. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Bonaventura, Antonella. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Garnero, Florencia Elizabeth. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina

HT-29 and Caco-2 Reporter Cell Lines for Functional Studies of Nuclear Factor Kappa B Activation

The NF-κB is a transcription factor which plays a key role in regulating biological processes. In response to signals, NF-κB activation occurs via phosphorylation of its inhibitor, which dissociates from the NF-κB dimer allowing the translocation to the nucleus, inducing gene expression. NF-κB activation has direct screening applications for drug discovery for several therapeutic indications. Thus, pathway-specific reporter cell systems appear as useful tools to screen and unravel the mode of action of probiotics and natural and synthetic compounds. Here, we describe the generation, characterization, and validation of human epithelial reporter cell lines for functional studies of NF-κB activation by different pro- and anti-inflammatory agents. Caco-2 and HT-29 cells were transfected with a pNF-κB-hrGFP plasmid which contains the GFP gene under the control of NF-κB binding elements. Three proinflammatory cytokines (TNF-α, IL-1β, and LPS) were able to activate the reporter systems in a dose-response manner, which corresponds to the activation of the NF-κB signaling pathway. Finally, the reporter cell lines were validated using lactic acid bacteria and a natural compound. We have established robust Caco-2-NF-κB-hrGFP and HT-29-NF-κB-hrGFP reporter cell lines which represent a valuable tool for primary screening and identification of bacterial strains and compounds with a potential therapeutic interest

Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity

CIGB-552 is a twenty-amino-acid novel synthetic peptide that has proven to be effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Such capability is conferred by its cell-penetrating peptide character, which allows it to enter cells and elicit a pro-apoptotic effect through its major mediator, COMMD1 protein. Cell-penetrating peptides are able to use different internalization mechanisms, such as endocytosis or direct transduction through the plasma membrane. Although CIGB-552 cytotoxicity has been evaluated in several non-tumor- and tumor-derived cell lines, no data regarding the relationship between cell line sensitivity, cell penetrating capacity, the internalization mechanisms involved, COMMD1 expression levels, or its subcellular localization has yet been produced. Here, we present the results obtained from a comparative analysis of CIGB-552 sensitivity, internalization capacity and the mechanisms involved in three human tumor-derived cell lines from different origins: mammary gland, colon and lung (MCF-7, HT-29 and H460, respectively). Furthermore, cell surface markers relevant for internalization processes such as phosphatidylserine, as well as CIGB-552 target COMMD1 expression/localization, were also evaluated. We found that both endocytosis and transduction are involved in CIGB-552 internalization in the three cell lines evaluated. However, CIGB-552 incorporation efficiency and contribution of each mechanism is cell-line dependent. Finally, sensitivity was directly correlated with high internalization capacity in those cell lines where endocytosis had a major contribution on CIGB-552 internalization

The Anticancer Peptide CIGB-552 Exerts Anti-Inflammatory and Anti-Angiogenic Effects through COMMD1

CIGB-552 is a synthetic anti-tumor peptide capable of reducing tumor size and increasing the lifespan of tumor-bearing mice. Part of its anti-cancer effects consists of inducing apoptosis, modulating NF-kB signaling pathway, and the angiogenesis process. Although one of its major mediators, the COMMD1 protein, has been identified, the mechanism by which CIGB-552 exerts such effects remains elusive. In the present study, we show the role of COMMD1 in CIGB-552 mechanism of action by generating the COMMD1 knock-out from the human lung cancer cell line NCI-H460. A microarray was performed to analyze both wild-type and KO cell lines with regard to CIGB-552 treatment. Additionally, different signaling pathways were studied in both cell lines to validate the results. Furthermore, the interaction between CIGB-552 and COMMD1 was analyzed by confocal microscopy. By signaling pathway analysis we found that genes involved in cell proliferation and apoptosis, oncogenic transformation, angiogenesis and inflammatory response are potentially regulated by the treatment with CIGB-552. We then demonstrated that CIGB-552 is capable of modulating NF-kB in both 2D and 3D cell culture models. Finally, we show that the ability of CIGB-552 to negatively modulate NF-kB and HIF-1 pathways is impaired in the COMMD1 knock-out NCI-H460 cell line, confirming that COMMD1 is essential for the peptide mechanism of action

Spectral phasor analysis of LAURDAN fluorescence in live A549 lung cells to study the hydration and time evolution of intracellular lamellar body-like structures.

International audienceUsing LAURDAN spectral imaging and spectral phasor analysis we concurrently studied the growth and hydration state of subcellular organelles (lamellar body-like, LB-like) from live A549 lung cancer cells at different post-confluence days. Our results reveal a time dependent two-step process governing the size and hydration of these intracellular LB-like structures. Specifically, a first step (days 1 to 7) is characterized by an increase in their size, followed by a second one (days 7 to 14) where the organelles display a decrease in their global hydration properties. Interestingly, our results also show that their hydration properties significantly differ from those observed in well-characterized artificial lamellar model membranes, challenging the notion that a pure lamellar membrane organization is present in these organelles at intracellular conditions. Finally, these LB-like structures show a significant increase in their hydration state upon secretion, suggesting a relevant role of entropy during this process

Effects of livestock exclusion on density, survival and biomass of the perennial sagebrush grass Hymenachne pernambucense (Poaceae) from a temperate fluvial wetland

In Argentina, the intensification of soybean production has displaced a substantial proportion of cattle ranching to fluvial wetlands such as those in the Delta of the Paraná River. Cattle grazing affects structure and dynamics of native forage plants but there is little information on this impact in populations from fluvial wetlands. This study addresses the effect of cattle ranching on density, survival, mean life-span and aerial biomass of Hymenachne pernambucense (Poaceae), an important forage species in the region. The study was carried out monthly for one year in permanents plots subject to continuous grazing and plots excluded from grazing in the Middle Delta of the Paraná River. In plots excluded from grazing, tillers showed significantly higher population density and survival, and a two-fold increase in mean life-span, while continuous grazing decreased survival of cohorts. The largest contribution to tiller density in ungrazed and grazed populations was made by spring and summer cohorts, respectively. Total and green biomass were significantly higher in the ungrazed population, with highest differences in late spring-early summer. Cattle grazing affected the relationship between tiller density and green biomass suggesting that cattle prefer sprouts because they are more palatable and nutritious than older tissue.Fil: Magnano, Andrea Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Instituto de Investigación en Ingeniería Ambiental; ArgentinaFil: Nanni, Analía Soledad. Universidad Nacional de San Martín. Instituto de Investigación en Ingeniería Ambiental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krug, Cecilia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Instituto de Investigación en Ingeniería Ambiental; ArgentinaFil: Astrada, Elizabeth Nora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Instituto de Investigación en Ingeniería Ambiental; ArgentinaFil: Vicari, Ricardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución; ArgentinaFil: Quintana, Ruben Dario. Universidad Nacional de San Martín. Instituto de Investigación en Ingeniería Ambiental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552

Because of resistance development by cancer cells against current anticancer drugs, there is a considerable interest in developing novel antitumor agents. We have previously demonstrated that CIGB-552, a novel cell-penetrating synthetic peptide, was effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Studies of protein–peptide interactions have shown that COMMD1 protein is a major mediator of CIGB-552 antitumor activity. Furthermore, a typical serine-protease degradation pattern for CIGB-552 in BALB/c mice serum was identified, yielding peptides which differ from CIGB-552 in size and physical properties. In the present study, we show the results obtained from a comparative analysis between CIGB-552 and its main metabolites regarding physicochemical properties, cellular internalization, and their capability to elicit apoptosis in MCF-7 cells. None of the analyzed metabolites proved to be as effective as CIGB-552 in promoting apoptosis in MCF-7. Taking into account these results, it seemed important to examine their cell-penetrating capacity and interaction with COMMD1. We show that internalization, a lipid binding-dependent process, is impaired as well as metabolite–COMMD1 interaction, key component of the apoptotic mechanism. Altogether, our results suggest that features conferred by the amino acid sequence are decisive for CIGB-552 biological activity, turning it into the minimal functional unit.Fil: Astrada, Soledad. Instituto Pasteur de Montevideo; UruguayFil: Gomez, Yolanda. Center For Genetic Engineering And Biotechnology; CubaFil: Barrera Guisasola, Exequiel Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Pasteur de Montevideo. Laboratorio de Simuladores Biomoleculares; UruguayFil: Obal, Gonzalo. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Pritsch, Otto. Instituto Pasteur de Montevideo; UruguayFil: Pantano, Sergio. Instituto Pasteur de Montevideo; UruguayFil: Vallespí, Maribel G.. Center For Genetic Engineering And Biotechnology; CubaFil: Bollati Fogolín, Mariela. Instituto Pasteur de Montevideo; Urugua

The transcriptional activities and cellular localization of the human estrogen receptor alpha are affected by the synonymous Ala87 mutation.

International audience: Until recently, synonymous mutations (which do not change amino acids) have been much neglected. Some evidence suggests that this kind of mutations could affect mRNA secondary structure or stability, translation kinetics and protein structure. To explore deeper the role of synonymous mutations, we studied their consequence on the functional activity of the estrogen receptor alpha (ERα). The ERα is a ligand-inducible transcription factor that orchestrates pleiotropic cellular effects, at both genomic and non-genomic levels in response to estrogens. In this work we analyzed in transient transfection experiments, the activity of ERα carrying the synonymous mutation Ala87, a polymorphism involving about 5-10% of the population. In comparison to the wild type receptor, our results show that ERαA87 mutation reduces the transactivation efficiency of ERα on an ERE reporter gene while its expression level remains similar. This mutation enhances 4-OHT-induced transactivation of ERα on an AP1 reporter gene. Finally, the mutation affects the subcellular localization of ERα in a cell type specific manner. It enhances the cytoplasmic location of ERα without significant changes in non-genomic effects of E2. The functional alteration of the ERαA87 determined in this work highlights the relevance of synonymous mutations for biomedical and pharmacological points of view