Differential gene expression signatures for cell wall integrity found in chitin synthase II (chs2Δ) and myosin II (myo1Δ) deficient cytokinesis mutants of Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Myosin II-dependent contraction of the cytokinetic ring and primary septum formation by chitin synthase II are interdependent processes during cytokinesis in <it>Saccharomyces cerevisiae</it>. Hence, null mutants of myosin II <it>(myo1</it>Δ<it>) </it>and chitin synthase II <it>(chs2</it>Δ<it>) </it>share multiple morphological and molecular phenotypes. To understand the nature of their interdependent functions, we will seek to identify genes undergoing transcriptional regulation in <it>chs2</it>Δ strains and to establish a transcription signature profile for comparison with <it>myo1</it>Δ strains.</p> <p>Results</p> <p>A total of 467 genes were commonly regulated between <it>myo1Δ </it>and <it>chs2Δ </it>mutant strains (p ≤ 0.01). Common regulated biological process categories identified by Gene Set Enrichment Analysis (GSEA) in both gene expression profiles were: protein biosynthesis, RNA processing, and stress response. Expression of 17/20 genes in the main transcriptional fingerprint for cell wall stress was confirmed in the <it>chs2Δ </it>strain versus 5/20 for the <it>myo1Δ </it>strain. One of these genes, <it>SLT2/MPK1</it>, was up-regulated in both strains and both strains accumulated the hyperphosphorylated form of Slt2p thereby confirming that the <it>PKC1 </it>cell wall integrity pathway (CWIP) was activated by both mutations. The <it>SLT2/MPK1 </it>gene, essential for <it>myo1Δ </it>strains, was not required in the <it>chs2Δ </it>strain.</p> <p>Conclusion</p> <p>Comparison of the <it>chs2Δ </it>and <it>myo1</it>Δ gene expression profiles revealed similarities in the biological process categories that respond to the <it>chs2Δ </it>and <it>myo1</it>Δ gene mutations. This supports the view that these mutations affect a common function in cytokinesis. Despite their similarities, these mutants exhibited significant differences in expression of the main transcriptional fingerprint for cell wall stress and their requirement of the CWIP for survival.</p

Homocysteine treatment alters redox capacity of both endothelial and tumor cells

Homocysteine is a non-proteinogenic amino acid playing key roles in two interconnected metabolic pathways, namely, the activated methyl cycle and the linear trans-sulfuration pathway that allows the conversion of methionine to cysteine. A dysregulation of intracellular homocysteine metabolism could yield an increased export of this amino acid, leading to hyperhomocysteinemia, which has been associated with an increased risk of cardiovascular diseases. In spite of decades of experimental effort, there is no definitive consensus on what could be the molecular mechanisms whereby hyperhomocysteinemia could contribute to cardiovascular disease. The redox active nature of homocysteine has favored the idea of an induction of oxidative stress as the underlying mechanism of homocysteine toxicity. In contrast, homocysteine can also behave as an anti-oxidant. The present work is aimed to further analyze the capacity of homocysteine to modulate the redox capacity of both endothelial and tumor cells. [Our experimental work is supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain)].Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Distortions associated with random sea simulators

[EN] Some numerical techniques for simulating Gaussian ergodic stochastic sea models are described, analyzed, and contrasted. A general method for generating all numerical, linear, one¿dimensional simulators by wave superposition permits one to describe or create any of these numerical random sea simulators in five steps. The distortions associated with each numerical simulator by wave superposition are analyzed from a general point of view and the arbitrariness of some numerical simulation techniques commonly used is noted. The time¿consumed in these Monte Carlo experiments is an important factor. The numerical algorithms used can change indirectly the level of distortions associated with each numerical simulation technique. A special reference has been made to the use of the fast Fourier transform (FFT) for computing and to the second¿order autoregressive behavior of each wave component in order to reduce the time¿consumed. Three criteria are proposed for qualifying the numerical simulators in order to adapt the requirements of each numerical experiment considered. To explain the variability of random sea, the deterministic amplitude component simulators are rejected while a nondeterministic spectral amplitude simulator (NSA) using a FFT algorithm can be employed.Medina, JR.; Aguilar Herrando, J.; Diez, JJ. (1985). Distortions associated with random sea simulators. Journal of Waterway Port Coastal and Ocean Engineering. 111(4):603-627. doi:10.1061/(ASCE)0733-950X(1985)111:4(603)S603627111

Transgenerational and within-generation plasticity shape thermal performance curves

Thermal performance curves (TPCs) compute the effects of temperature on the performance of ectotherms and are frequently used to predict the effect of environmental conditions and currently, climate change, on organismal vulnerability and sensitivity. Using Drosophila melanogaster as an animal model, we examined how different thermal environments affected the shape of the performance curve and their parameters. We measured the climbing speed as a measure of locomotor performance in adult flies and tested the ontogenetic and transgenerational effects of thermal environment on TPC shape. Parents and offspring were reared at 28 ± 0ºC (28C), 28 ± 4ºC (28V), and 30 ± 0ºC (30C). We found that both, environmental thermal variability (28V) and high temperature (30C) experienced during early ontogeny shaped the fruit fly TPC sensitivity. Flies reared at variable thermal environments shifted the TPC to the right and increased heat tolerance. Flies held at high and constant temperature exhibited lower maximum performance than flies reared at the variable thermal environment. Furthermore, these effects were extended to the next generation. The parental thermal environment had a significative effect on TPC and its parameters. Indeed, flies reared at 28V whose parents were held at a high and constant temperature (30C) had a lower heat tolerance than F1 of flies reared at 28C or 28V. Also, offspring of flies reared at variable thermal environment (28V) reached the maximum performance at a higher temperature than offspring of flies reared at 28C or 30C. Consequently, since TPC parameters are not fixed, we suggest cautiousness when using TPCs to predict the impact of climate change on natural populations.Fil: Cavieres Parada, Grisel Beatriz. Pontificia Universidad Católica de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; ArgentinaFil: Alruiz, José M.. Pontificia Universidad Católica de Chile; ChileFil: Medina, Nadia R.. Pontificia Universidad Católica de Chile; ChileFil: Bogdanovich, José M.. Pontificia Universidad Católica de Chile; ChileFil: Bozinovic, Francisco. Pontificia Universidad Católica de Chile; Chil

Promoting higher added value to a finfish species rejected to sea

332 páginas.-- José Ramón Fuertes ... et al.This project aimed to the development of the research and the technology necessary to promote higher added value to fishing activity. This is to be achieved by obtaining profit from a finfish species (“Rockcod”, Patagonotothen spp.) not known to consumers and currently discarded by the EU fishing fleet operating in the South West Atlantic, in order to supply the EU seafood industry with a good quality raw material for human food manufacturing. Use of this species, caught as a by-catch in the existing fisheries targeting hakes and cephalopods, should also increase the profitability of the fleet, contribute to maintaining employment and help to counterbalance the negative effects of fishing activity and discards in the ecosystem. The main scientific-technological objectives and expected achievements were the following: - Description of the fisheries - Improved knowledge of the biology of the species - Biomass assessment - Estimation of catches and discards - Analysis of the spatial and temporal distribution of the resource. Fishery forecasting and testing - Sensorial, Microbiological, Nutritional and Biochemical Evaluation of Rock cod - Development of the technical modifications on board commercial vessels - Development of new processed products from frozen Rock codContract number Q5CR-2002-71709Peer reviewe

Dopamine D4 receptor activation counteracts nigrostriatal pathway activation by morphine: relevance in drug addiction.

Morphine induces dopamine release in the caudate putamen (CPu), which promotes stereotyped behavior and habit learning for drug-seeking and –taking. Nigrostriatal pathway stimulation by morphine is due to a removal of tonic inhibition arising from SNr GABA interneurons on SNc dopaminergic neurons through the mu opioid receptor (MOR). Long-term morphine exposure produces a series of adaptations in SNc dopamine neurons, which affect neuron excitability and dopamine output to CPu. We have previously shown that dopamine D4 receptor (D4R) stimulation counteracts acute and chronic morphine-induced accumulation of several transcription factors in the CPu (Gago et al., 2011 Brain Res.). Since D4R is expressed in the SNr (Rivera et al., Brain Res. 2003), we postulate that a functional D4R-MOR interaction at the midbrain level could exists. We have investigated the role of D4R in the morphine-induced nigroestriatal dopamine metabolism in the rat brain using biochemical and immunohistochemical techniques. We also have studied the influence of D4R on morphine-induced morphological changes in SNc dopamine neurons using both immunohistochemical and image analysis techniques. Finally, we examined a possible underlying mechanism of the D4R-MOR interaction at the SN level using in vitro quantitative receptor autoradiography. We have found that D4R activation restores dopamine metabolism in the nigroestriatal pathway after acute morphine treatment and prevents morphine-induced rise of tyroxine hydroxylase and dopamine transporter. Rats receiving a continuous treatment of morphine (6 days) showed SNc dopamine neurons with smaller size and higher circularity index compared with the controls animals. These morphine-induced morphological adaptatives changes were prevented when a D4R agonist (PD168,077) was administered at the same time with morphine. Autoradiographic studies demonstrated that the D4R agonist reduce the affinity of MOR. The present study provides evidence for the existence of a fully blocking effect of the D4R on the activation of dopaminergic nigroestriatal pathway by morphine.Financiación: P09-CVI- 4702 (Proyecto de Excelencia de la Junta de Andalucía

El costo de capital y su incidencia en los métodos de flujo de caja descontados

A techno-economic feasibility study in any branch of engineering or any kind of business involves knowing a measure of the investment profitability. Currently, no one discuss that for a solid basis decision making it should be used discounted cash flow (DCF), despite the persistence of a widespread forms (i.e. payback period, benefit / cost). The objective of this paper is to analyze, critically, the relevance of the methods used to make comparisons between mutually exclusive projects as well as suggest alternative ways of analysis that consider the impact of different rates of capital cost and constrain the decision in an appropriate way. The proposal presented here allows exclusive alternatives ordering with an approach that include a more complete view on the problem. The most interesting result is related to the sensitivity of the methods on the inherent decision variables involved in them.DOI: http://dx.doi.org/10.5377/nexo.v25i1.793 Nexo Revista Científica,Vol. 25, No. 01, pp.18-21/Junio 2012 Un estudio de factibilidad técnico económico en cualquier rama de la ingeniería o en cualquier tipo de negocio, implica conocer una medida de la rentabilidad del emprendimiento. Actualmente, nadie discute que para una toma de decisión fundamentada se deben utilizar los métodos de flujo de caja descontados (DCF), a pesar de que persisten otras formas muy difundidas (por ejemplo: período de repago, relación beneficio/costo). El objetivo del trabajo es analizar críticamente los métodos a utilizar para evaluar proyectos mutuamente excluyentes, como también proponer formas alternativas de análisis de rentabilidad que contemplen la incidencia de las distintas tasas y acoten la decisión de un modo adecuado. La propuesta presentada aquí permite ordenar alternativas excluyentes con criterios que contengan una visión mas completa. El resultado más interesante está relacionado con la sensibilidad de los métodos sobre las variables de decisión inherentes a estos.DOI: http://dx.doi.org/10.5377/nexo.v25i1.793 Nexo Revista Científica,Vol. 25, No. 01, pp.18-21/Junio 2012

Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation

Neural progenitor cells (NPCs) are self-renewing cells that give rise to the major cells in the nervous system and are considered to be the possible cell of origin of glioblastoma. The gap junction protein connexin43 (Cx43) is expressed by NPCs, exerting channel-dependent and -independent roles. We focused on one property of Cx43-its ability to inhibit Src, a key protein in brain development and oncogenesis. Because Src inhibition is carried out by the sequence 266-283 of the intracellular C terminus in Cx43, we used a cell-penetrating peptide containing this sequence, TAT-Cx43266-283, to explore its effects on postnatal subventricular zone NPCs. Our results show that TAT-Cx43266-283 inhibited Src activity and reduced NPC proliferation and survival promoted by epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). In differentiation conditions, TAT-Cx43266-283 increased astrocyte differentiation at the expense of neuronal differentiation, which coincided with a reduction in Src activity and β-catenin expression. We propose that Cx43, through the region 266-283, reduces Src activity, leading to disruption of EGF and FGF-2 signaling and to down-regulation of β-catenin with effects on proliferation and differentiation. Our data indicate that the inhibition of Src might contribute to the complex role of Cx43 in NPCs and open new opportunities for further research in gliomagenesis.FEDER RTI2018-099873-B-I00/Ministerio de Ciencia, Innovación y Universidades Rocío Talaverón fellowship/Fundación Científica Asociación Española Contra el Cáncer PGC20185-094654-B-100/Ministerio de Ciencia, Innovación y Universidade