Prediction of gene essentiality using machine learning and genome-scale metabolic models

The identification of essential genes, i.e. those that impair cell survival when deleted, requires large growth assays of knock-out strains. The complexity and cost of such experiments has triggered a growing interest in computational methods for prediction of gene essentiality. In the case of metabolic genes, Flux Balance Analysis (FBA) is widely employed to predict essentiality under the assumption that cells maximize their growth rate. However, this approach assumes that knock-out strains optimize the same objectives as the wild-type, which excludes cases in which deletions cause large physiological changes to meet other objectives for survival. Here, we resolve this limitation with a novel machine learning approach that predicts essentiality directly from wild-type flux distributions. We first project the wild-type FBA solution onto a mass flow graph, a digraph with reactions as nodes and edge weights proportional to the mass transfer between reactions, and then train binary classifiers on the connectivity of graph nodes. We demonstrate the efficacy of this approach using the most complete metabolic model of Escherichia coli, achieving near state-of-the art prediction accuracy for essential genes. Our approach suggests that wild-type FBA solutions contain enough information to predict essentiality, without the need to assume optimality of deletion strains

H^+_2$ in a strong magnetic field described via a solvable model

We consider the hydrogen molecular ion $H^+_2$ in the presence of a strong homogeneous magnetic field. In this regime, the effective Hamiltonian is almost one dimensional with a potential energy which looks like a sum of two Dirac delta functions. This model is solvable, but not close enough to our exact Hamiltonian for relevant strenght of the magnnetic field. However we show that the correct values of the equilibrium distance as well as the binding energy of the ground state of the ion, can be obtained when incorporating perturbative corrections up to second order. Finally, we show that $He_2^{3+}$ exists for sufficiently large magnetic fields

Burdigalian deposits of the Santa Cruz Formation in the Sierra Baguales, Austral (Magallanes) Basin: Age, depositional environment and vertebrate fossils

Indexación: Web of Science; Scielo.ABSTRACT. A succession of marine and continental strata on the southern flank of Cerro Cono in the Sierra Baguales, northeast of Torres del Paine, can be correlated with stratigraphic units exposed along the southern border of the Lago Argentino region in Santa Cruz Province, Argentina. These include the Estancia 25 de Mayo Formation and the basal part of the Santa Cruz Formation. The lithological correlation is also confirmed by detrital zircon ages (maximum age of 18.23±0.26 Ma) and a rich assemblage of terrestrial vertebrate fossils, biostratigraphically equivalent to a postColhuehuapian, pre-Santacrucian South American Land Mammal Age (SALMA) fauna, suggesting a range of 19 to 17.8 Ma. Similar ages have been obtained from the basal part of the Santa Cruz Formation at Estancia Quién Sabe in southwestern Argentina, supporting the assumption of a regional continuity between these deposits. A measured lithostratigraphic column is presented and the depositional environment is interpreted as a coastal plain with small, meandering rivers and ephemeral floodplain lakes. The sedimentation coincides with intensified uplift of the Patagonian Andes during the ‘Quechua Phase’ of Andean tectonism, which is reflected by a change in paleocurrent directions from northwest to east-northeast. Keywords: Burdigalian, Santa Cruz Formation, Santacrucian SALMA, ‘Notohippidian’ fauna, Meandering rivers.RESUMEN. Una sucesión de estratos marinos y continentales en el flanco meridional del cerro Cono, en la sierra Baguales, al noreste de Torres del Paine, se correlaciona con estratos al sur de la región de lago Argentino en la Provincia de Santa Cruz, República Argentina. Estas unidades incluyen la Formación Estancia 25 de Mayo y la parte basal de la Formación Santa Cruz. La correlación litológica es, además, confirmada por datación de circones detríticos (edad máxima de 18,23±0,26 Ma) y un variado ensamble de vertebrados fósiles terrestres de edad post-Colhuehuapense a pre-Santacrucense en la escala de Edades Mamífero Sudamericanas (EMAS), con un rango temporal de entre 19 a 17,8 Ma. Edades similares han sido reportadas para la parte basal de la Formación Santa Cruz, en estancia Quién Sabe, en el suroeste de Argentina, ratificando la continuidad regional entre estos depósitos. Se presenta una columna estratigráfica y se interpreta el ambiente de depositación como una llanura costera con pequeños ríos sinuosos y lagos efímeros. La edad de sedimentación coincide con el solevantamiento de los Andes Patagónicos durante la 'Fase Quechua', lo que se ve reflejado por un cambio en la dirección de las paleocorrientes desde el noroeste hacia el este-noreste.http://ref.scielo.org/csxwd

Revised timing of cenozoic atlantic incursions and changing hinterland sediment sources during southern patagonian orogenesis

New detrital zircon U-Pb geochronology data from the Cenozoic Magallanes-Austral Basin in Argentina and Chile ~51° S establish a revised chronostratigraphy of Paleocene-Miocene foreland synorogenic strata and document the rise and subsequent isolation of hinterland sources in the Patagonian Andes from the continental margin. The upsection loss of zircons derived from the hinterland Paleozoic and Late Jurassic sources between ca. 60 and 44Ma documents a major shift in sediment routing due to Paleogene orogenesis in the greater Patagonian-Fuegian Andes. Changes in the proportion of grains from hinterland thrust sheets, comprised of Jurassic volcanics and Paleozoic metasedimentary rocks, provide a trackable signal of long-term shifts in orogenic drainage divide and topographic isolation due to widening of the retroarc fold-thrust belt. The youngest detrital zircon U-Pb ages confirm timing of Maastrichtian-Eocene strata but require substantial age revisions for part of the overlying Cenozoic basinfill during the late Eocene and Oligocene. The upper Río Turbio Formation, previously mapped as middle to late Eocene in the published literature, records a newly recognized latest Eocene-Oligocene (37-27Ma) marine incursion along the basin margin. We suggest that these deposits could be genetically linked to the distally placed units along the Atlantic coast, including the El Huemul Formation and the younger San Julián Formation, via an eastward deepening within the foreland basin system that culminated in a basin-wide Oligocene marine incursion in the Southern Andes. The overlying Río Guillermo Formation records onset of tectonically generated coarse-grained detritus ca. 24.3Ma and a transition to the first fully nonmarine conditions on the proximal Patagonian platform since Late Cretaceous time, perhaps signaling a Cordilleran-scale upper plate response to increased plate convergence and tectonic plate reorganization.Fil: Fosdick, Julie C.. University of Connecticut; Estados UnidosFil: VanderLeest, R. A.. University of Connecticut; Estados UnidosFil: Bostelmann, J. E.. Universidad de Chile; ChileFil: Leonard, J. S.. Arizona State University; Estados UnidosFil: Ugalde, R.. Universidad Mayor; ChileFil: Oyarzún, J. L.. Parque Geo-paleontológico la Cumbre-baguales; ChileFil: Griffin, Miguel. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleozoología Invertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Synthesis and morphological characterization of nanocomposite based on anodic TiO2 nanotubes and poly(N-maleoyl Glycine-CO-Acrylic acid)

Indexación: Scopus.In this study, we examined the synthesis, and characterization of TiO2/poly(N-maleoylglycine-co-acrylic acid) (TiO2/poly(MG-co-AA)) nanocomposite. The nanocomposite was prepared by the dispersion of TiO2 nanotubes in a water solution of the polymer (3% w/w) and then it was lyophilized. The nanocomposite was characterized by FTIR and Raman spectroscopies. The incorporation of TiO2 nanotubes to the polymeric matrix was determined by transmission electron microscopy (TEM) from which TiO2 nanotubes in the inner of copolymer with diameters ranging between 90 and 100 nm were observed. The overall morphology of the previously synthetized nanotubes was determined by scanning electron microscopy (SEM). For the nanocomposite system, the morphology was studied by atomic force microscopy (AFM) from which a grain shape structure was observed. This process resulted in a new nanocompsite material with an average grain diameter estimated by SEM and AFM ranging between 210-240 nm. It was observed that the nanotubes were homogeneously dispersed within the polymeric matrix. The prepared material could be suitable in the design of electronic devices and additionally could have potential applications as biomaterial.https://scielo.conicyt.cl/pdf/jcchems/v62n3/0717-9324-jcchems-62-03-3634.pd

Nutritional Immunity Triggers the Modulation of Iron Metabolism Genes in the Sub-Antarctic Notothenioid Eleginops maclovinus in Response to Piscirickettsia salmonis

Iron deprivation is a nutritional immunity mechanism through which fish can limit the amount of iron available to invading bacteria. The aim of this study was to evaluate the modulation of iron metabolism genes in the liver and brain of sub-Antarctic notothenioid Eleginops maclovinus challenged with Piscirickettsia salmonis. The specimens were inoculated with two P. salmonis strains: LF-89 (ATCC® VR-1361™) and Austral-005 (antibiotic resistant). Hepatic and brain samples were collected at intervals over a period of 35 days. Gene expression (by RT-qPCR) of proteins involved in iron storage, transport, and binding were statistically modulated in infected fish when compared with control counterparts. Specifically, the expression profiles of the transferrin and hemopexin genes in the liver, as well as the expression profiles of ferritin-M, ferritin-L, and transferrin in the brain, were similar for both experimental groups. Nevertheless, the remaining genes such as ferritin-H, ceruloplasmin, hepcidin, and haptoglobin presented tissue-specific expression profiles that varied in relation to the injected bacterial strain and sampling time-point. These results suggest that nutritional immunity could be an important immune defense mechanism for E. maclovinus against P. salmonis injection. This study provides relevant information for understanding iron metabolism of a sub-Antarctic notothenioid fish

Control structure and limitations of biochemical networks

Abstract-Biochemical networks typically exhibit intricate topologies that hinder their analysis with control-theoretic tools. In this work we present a systematic methodology for the identification of the control structure of a reaction network. The method is based on a bandwidth reduction technique applied to the incidence matrix of the network's graph. In addition, in the case of mass-action and stable networks we show that it is possible to identify linear algebraic dependencies between the time-domain integrals of some species' concentrations. We consider the extrinsic apoptosis pathway and an activationinhibition mechanism to illustrate the application of our results

Control structure and limitations of biochemical networks

Abstract-Biochemical networks typically exhibit intricate topologies that hinder their analysis with control-theoretic tools. In this work we present a systematic methodology for the identification of the control structure of a reaction network. The method is based on a bandwidth reduction technique applied to the incidence matrix of the network's graph. In addition, in the case of mass-action and stable networks we show that it is possible to identify linear algebraic dependencies between the time-domain integrals of some species' concentrations. We consider the extrinsic apoptosis pathway and an activationinhibition mechanism to illustrate the application of our results