Manipulation of Mitochondria Dynamics Reveals Separate Roles for Form and Function in Mitochondria Distribution

Mitochondria shape is controlled by membrane fusion and fission mediated by mitofusins, Opa1, and Drp1, whereas mitochondrial motility relies on microtubule motors. These processes govern mitochondria subcellular distribution, whose defects are emphasized in neurons because of their polarized structure. We have studied how perturbation of the fusion/fission balance affects mitochondria distribution in Drosophila axons. Knockdown of Marf or Opa1 resulted in progressive loss of distal mitochondria and in a distinct oxidative phosphorylation and membrane potential deficit. Downregulation of Drp1 rescued the lethality and bioenergetic defect caused by neuronal Marf RNAi, but induced only a modest restoration of axonal mitochondria distribution. Surprisingly, Drp1 knockdown rescued fragmentation and fully restored aberrant distribution of axonal mitochondria produced by Opa1 RNAi; however, Drp1 knockdown did not improve viability or mitochondria function. Our data show that proper morphology is critical for proper axonal mitochondria distribution independent of bioenergetic efficiency. The health of neurons largely depends on mitochondria function, but does not depend on shape or distribution. Trevisan et al. separate the independent contribution of form and function in determining the distribution of mitochondria in axons. They show that morphology is crucial for proper axonal mitochondria distribution, independent of their bioenergetic efficiency. However, the health of neurons depends on mitochondria function, but does not depend on shape or distributio

Synthesis of biotechnological processes using generalized disjunctive programming

This article presents a model for the synthesis of a biotechnological process in which a set of biotechnological products must be elaborated. For each of these products, there is a set of hosts that can be used for production. According to the host selected for each product, there is a different set of stages involved in the process. Furthermore, to carry out the task involved at a particular stage, there are different units that can be selected. Depending on the kind of equipment used, different performances can be obtained in terms of the stage yield, dimension required by the unit, processing time, etc. A generalized disjunctive programming model is formulated to solve this problem. This problem is transformed into an MINLP using either a big-M or convex hull reformulation. Both alternatives are solved, and their performances are evaluated.Fil: Montagna, Jorge Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; ArgentinaFil: Iribarren, Oscar Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; ArgentinaFil: Vecchietti, Aldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; Argentin

The role of process variables in the design of multiproduct batch protein production plants

This work reports findings about the role of process variables in the design of multiproduct batch plants. Unlike continuous processes, batch processes are subject to size and time constraints which depend on the structure of the plant: the number of units at each stage and the provision of intermediate storage. We used simple process performance models (yet involving all the process variables with significant economic impact) to get explicit expressions for these size and time factors. The traditional approach uses fixed size and time factors. So the addition of those expressions to the original fixed factors model, permitted to simultaneously optimize the plant structure and process variables, and study the role of the latter in the design. We found that if the plant structure constraints are disregarded (with a Free Unlimited Storage operating policy), process variables behave just alike in continuous processes. They trade off cost components with the Total Annual Cost being quite insensitive to them in the neighborhood of the optimal solution. As setting the process variables sets the size and time factors, this means that near the optimal set of process variables, cycle times and size factors can be accommodated to the plant structure, with little effect on the cost of equipment.Fil: Montagna, Jorge Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; ArgentinaFil: Vecchietti, Aldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; ArgentinaFil: Iribarren, Oscar Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; ArgentinaFil: Pinto, José M.. Universidade de Sao Paulo; BrasilFil: Asenjo, Juan A.. Universidad de Chile; Chil

Impacto económico-ambiental del planeamiento estratégico de inversiones en el sector energético de la Argentina

En este trabajo se presenta un programa de optimización multiperíodo para analizar un plan estratégico de inversiones en el sector energético, que tiene en cuenta los recursos naturales renovables y no-renovables disponibles en la región. El objetivo es ponderar las inversiones desde el punto de vista económico y el ambiental. Este último medido a través de la emisión de gases de efecto invernadero y su apreciación por medio de los bonos de carbono. Se presentan los resultados obtenidos en la evaluación de diversos escenarios con el objeto de realizar un análisis de sensibilidad respecto del valor de mercado de los bonos de carbono y el aumento de reservas de gas natural.Sociedad Argentina de Informática e Investigación Operativ

Impacto económico-ambiental del planeamiento estratégico de inversiones en el sector energético de la Argentina

En este trabajo se presenta un programa de optimización multiperíodo para analizar un plan estratégico de inversiones en el sector energético, que tiene en cuenta los recursos naturales renovables y no-renovables disponibles en la región. El objetivo es ponderar las inversiones desde el punto de vista económico y el ambiental. Este último medido a través de la emisión de gases de efecto invernadero y su apreciación por medio de los bonos de carbono. Se presentan los resultados obtenidos en la evaluación de diversos escenarios con el objeto de realizar un análisis de sensibilidad respecto del valor de mercado de los bonos de carbono y el aumento de reservas de gas natural.Sociedad Argentina de Informática e Investigación Operativ

Impacto económico-ambiental del planeamiento estratégico de inversiones en el sector energético de la Argentina

En este trabajo se presenta un programa de optimización multiperíodo para analizar un plan estratégico de inversiones en el sector energético, que tiene en cuenta los recursos naturales renovables y no-renovables disponibles en la región. El objetivo es ponderar las inversiones desde el punto de vista económico y el ambiental. Este último medido a través de la emisión de gases de efecto invernadero y su apreciación por medio de los bonos de carbono. Se presentan los resultados obtenidos en la evaluación de diversos escenarios con el objeto de realizar un análisis de sensibilidad respecto del valor de mercado de los bonos de carbono y el aumento de reservas de gas natural.Sociedad Argentina de Informática e Investigación Operativ

Modelo matemático para la planificación de las inversiones en fuentes de energía renovables para la Argentina

En este trabajo se presenta un programa matemático mixto-entero lineal (MILP) multiperiodo para planificar las inversiones en fuentes de energía convencionales y renovables, con énfasis en estas últimas. Se consideran aquellas que presentan una mayor ventaja competitiva para la Argentina y cuyas tecnologías han alcanzado una cierta madurez y confiabilidad. El horizonte de tiempo de trabajo propuesto es de 20 años. El modelo busca minimizar los costos de inversión y operación de las fuentes de energía y permite realizar un análisis de escenarios variando las hipótesis del mismo. Los resultados que brinda el modelo permiten visualizar las inversiones realizadas, cómo afectan las mismas a la composición de la matriz energética, los momentos en que se deciden las inversiones así como sus montos.Sociedad Argentina de Informática e Investigación Operativ

Pancreatic cancer spheres are more than just aggregates of stem marker-positive cells

Pancreatic cancer stem-like cells are described by membrane expression of CD24, CD44 and ESA (epithelial-specific antigen) and their capacity to grow as spheres in a serum-free medium containing well-defined growth factors. The capacity of a panel of four pancreatic cancer cell lines (PANC-1, CFPAC-1, PancTu-1 and PSN-1) to form spheres was tested. All cell lines with the exception of PancTu-1 developed spheres. Phenotypically, the sphere-growing cells showed an increased in vitro invasion capability. Both gene and protein expressions of markers of metastases [CXCR4 (CXC chemokine receptor 4), OPN (osteopontin) and CD44v6] and components of active hedgehog pathway signalling were assessed. Spheres clearly demonstrated increased expression of the above-mentioned markers when compared with their adherent counterpart. With the aim of identifying a minimum set of markers able to separate cells that have the capacity to form spheres from those incapable of forming spheres, a PCA (principal component analysis) of the multidimensional dataset was performed. Although PCA of the ‘accepted’ stemness genes was unable to separate sphere-forming from sphere-incapable cell lines, the addition of the ‘aggressiveness’ marker CD44v6 allowed a clear differentiation. Moreover, inoculation of the spheres and the adherent cells in vivo confirmed the superior aggressiveness (proliferation and metastasis) of the spheres over the adherent cells. In conclusion, the present study suggests that the sphere-growing cell population is not only composed of cells displaying classical stem membrane markers but also needs CD44v6-positive cells to successfully form spheres. Our results also emphasize the potential therapeutic importance of pathways such as CXCR4 and hedgehog for pancreatic cancer treatment

Dynamic constriction andfission of endoplasmicreticulum membranes by reticulon

The endoplasmic reticulum (ER) is a continuous cell-wide membrane network. Network formation has been associated with proteins producing membrane curvature and fusion, such as reticulons and atlastin. Regulated network fragmentation, occurring in different physiological contexts, is less understood. Here we find that the ER has an embedded fragmentation mechanism based upon the ability of reticulon to produce fission of elongating network branches. In Drosophila, Rtnl1-facilitated fission is counterbalanced by atlastin-driven fusion, with the prevalence of Rtnl1 leading to ER fragmentation. Ectopic expression of Drosophila reticulon in COS-7 cells reveals individual fission events in dynamic ER tubules. Consistently, in vitro analyses show that reticulon produces velocity-dependent constriction of lipid nanotubes leading to stochastic fission via a hemifission mechanism. Fission occurs at elongation rates and pulling force ranges intrinsic to the ER, thus suggesting a principle whereby the dynamic balance between fusion and fission controlling organelle morphology depends on membrane motility.This work was partially supported by NIH R01GM121725 to V.A.F., a 5x1000 grant from the Italian Ministry of Health and Telethon GGP11189 to A.D., Spanish Ministry of Science, Innovation and Universities grants BFU2015-70552-P to V.A.F. and A.V.S., and BFU2015-63714-R and PGC2018-099341-B-I00 to B.I., Basque Government grant IT1196-19, Russian Science Foundation Grant No. 17-75-30064 and Ministry of Science and Higher Education of the Russian Federation

Hypomelanosis of Ito with a trisomy 2 mosaicism: a case report

Introduction: Hypomelanosis of Ito is a rare neurocutaneous disorder, characterized by streaks and swirls of hypopigmentation following the lines of Blaschko that may be associated to systemic abnormalities involving the central nervous system and musculoskeletal system. Despite the preponderance of reported sporadic hypomelanosis of Ito, few reports of familial hypomelanosis of Ito have been described. Case presentation: A 6-month-old Caucasian girl presented with unilateral areas of hypomelanosis distributed on the left half of her body and her father presented with similar mosaic hypopigmented lesions on his upper chest. Whereas both blood karyotypes obtained from peripheral lymphocyte cultures were normal, a 16% trisomy 2 mosaicism was found in cultured skinfibroblasts derived from a hypopigmented skin area of her father. Conclusions: Familial cases of hypomelanosis of Ito are very rare and can occur in patients without systemic involvement. Hypomelanosis of Ito constitutes a non-specific diagnostic definition including different clinical entities with a wide phenotypic variability, either sporadic or familial. Unfortunately, a large number of cases remain misdiagnosed due to both diagnostic challenges and controversial issues on cutaneous biopsies in the pediatric population