Nuclear Analyses for the Assessment of the Loads on the ITER Radial Neutron Camera In-Port System and Evaluation of Its Measurement Performances

The radial neutron camera (RNC) is a key ITER diagnostic system designed to measure the uncollided 14- and 2.5-MeV neutrons from deuterium-tritium (DT) and deuterium-deuterium (DD) fusion reactions, through an array of detectors covering a full poloidal plasma section along collimated lines of sight (LoS). Its main objective is the assessment of the neutron emissivity/alpha source profile and the total neutron source strength, providing spatially resolved measurements of several parameters needed for fusion power estimation, plasma control, and plasma physics studies. The present RNC layout is composed of two fan-shaped collimating structures viewing the plasma radially through vertical slots in the diagnostic shielding module (DSM) of ITER Equatorial Port 1 (EP01): the ex-port subsystem and the in-port one. The ex-port subsystem, devoted to the plasma core coverage, extends from the Port Interspace to the Bioshield Plug: it consists of a massive shielding unit hosting two sets of collimators lying on different toroidal planes, leading to a total of 16 interleaved LoS. The in-port system consists of a cassette, integrated inside the port plug DSM, containing two detectors per each of the six LoS looking at the plasma edges. The in-port system must guarantee the required measurement performances in critical operating conditions in terms of high radiation levels, given its proximity to the plasma neutron source. This article presents an updated neutronic analysis based on the latest design of the in-port system and port plug. It has been performed by means of the Monte Carlo MCNP code and provides nuclear loads on the in-port RNC during normal operating conditions (NOC) and inputs for the measurement performance analysis

Strong signatures of selection in the domestic pig genome

Domestication of wild boar (Sus scrofa) and subsequent selection have resulted in dramatic phenotypic changes in domestic pigs for a number of traits, including behavior, body composition, reproduction, and coat color. Here we have used whole-genome resequencing to reveal some of the loci that underlie phenotypic evolution in European domestic pigs. Selective sweep analyses revealed strong signatures of selection at three loci harboring quantitative trait loci that explain a considerable part of one of the most characteristic morphological changes in the domestic pig—the elongation of the back and an increased number of vertebrae. The three loci were associated with the NR6A1, PLAG1, and LCORL genes. The latter two have repeatedly been associated with loci controlling stature in other domestic animals and in humans. Most European domestic pigs are homozygous for the same haplotype at these three loci. We found an excess of derived nonsynonymous substitutions in domestic pigs, most likely reflecting both positive selection and relaxed purifying selection after domestication. Our analysis of structural variation revealed four duplications at the KIT locus that were exclusively present in white or white-spotted pigs, carrying the Dominant white, Patch, or Belt alleles. This discovery illustrates how structural changes have contributed to rapid phenotypic evolution in domestic animals and how alleles in domestic animals may evolve by the accumulation of multiple causative mutations as a response to strong directional selection

Selection for environmental variance of litter size in rabbits

[EN] Background: In recent years, there has been an increasing interest in the genetic determination of environmental variance. In the case of litter size, environmental variance can be related to the capacity of animals to adapt to new environmental conditions, which can improve animal welfare. Results: We developed a ten-generation divergent selection experiment on environmental variance. We selected one line of rabbits for litter size homogeneity and one line for litter size heterogeneity by measuring intra-doe phenotypic variance. We proved that environmental variance of litter size is genetically determined and can be modified by selection. Response to selection was 4.5% of the original environmental variance per generation. Litter size was consistently higher in the Low line than in the High line during the entire experiment. Conclusions: We conclude that environmental variance of litter size is genetically determined based on the results of our divergent selection experiment. This has implications for animal welfare, since animals that cope better with their environment have better welfare than more sensitive animals. We also conclude that selection for reduced environmental variance of litter size does not depress litter size.This research was funded by the Ministerio de Economía y Competitividad (Spain), Projects AGL2014-55921, C2-1-P and C2-2-P. Marina Martínez-Alvaro has a Grant from the same funding source, BES-2012-052655.Blasco Mateu, A.; Martínez Álvaro, M.; García Pardo, MDLL.; Ibáñez Escriche, N.; Argente, MJ. (2017). Selection for environmental variance of litter size in rabbits. Genetics Selection Evolution. 49(48):1-8. https://doi.org/10.1186/s12711-017-0323-4S184948Morgante F, Sørensen P, Sorensen DA, Maltecca C, Mackay TFC. Genetic architecture of micro-environmental plasticity in Drosophila melanogaster. Sci Rep. 2015;5:9785.Sørensen P, de los Campos G, Morgante F, Mackay TFC, Sorensen D. 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Effect of selection for residual variance of litter size on hematology parameters as immunology indicators in rabbits. In: Proceedings of the 10th World Congress on genetics applied to livestock production. Vancouver; 2014.García ML, Zbynovska K, Petruska P, Bovdisová I, Kalafová A, Capcarova M, et al. Effect of selection for residual variance of litter size on biochemical parameters in rabbits. In: Proceedings of the 67th annual meeting of the European Federation of Animal Science. Belfast; 2016.Broom DM. Welfare assessment and relevant ethical decisions: key concepts. Annu Rev Biomed Sci. 2008;20:79–90.SanCristobal-Gaudy M, Bodin L, Elsen JM, Chevalet C. Genetic components of litter size variability in sheep. Genet Sel Evol. 2001;33:249–71.Sorensen D, Waagepetersen R. Normal linear models with genetically structured residual variance heterogeneity: a case study. Genet Res. 2003;82:207–22.Mulder HA, Hill WG, Knol EF. Heritable environmental variance causes nonlinear relationships between traits: application to birth weight and stillbirth of pigs. Genetics. 2015;199:1255–69.Ros M, Sorensen D, Waagepetersen R, Dupont-Nivet M, San Cristobal M, Bonnet JC. Evidence for genetic control of adult weight plasticity in the snail Helix aspersa. Genetics. 2004;168:2089–97.Gutiérrez JP, Nieto B, Piqueras P, Ibáñez N, Salgado C. Genetic parameters for components analysis of litter size and litter weight traits at birth in mice. Genet Sel Evol. 2006;38:445–62.Ibáñez-Escriche N, Sorensen D, Waagepetersen R, Blasco A. Selection for environmental variation: a statistical analysis and power calculations to detect response. Genetics. 2008;180:2209–26.Wolc A, White IM, Avendano S, Hill WG. Genetic variability in residual variation of body weight and conformation scores in broiler chickens. Poult Sci. 2009;88:1156–61.Fina M, Ibáñez-Escriche N, Piedrafita J, Casellas J. Canalization analysis of birth weight in Bruna dels Pirineus beef cattle. J Anim Sci. 2013;91:3070–8.Mulder HA, Rönnegård L, Fikse WF, Veerkamp RF, Strandberg E. Estimation of genetic variance for macro- and micro-environmental sensitivity using double hierarchical generalized linear models. Genet Sel Evol. 2013;45:23.Janhunen M, Kause A, Vehviläinen H, Järvisalom O. Genetics of microenvironmental sensitivity of body weight in rainbow trout (Oncorhynchus mykiss) selected for improved growth. PLoS One. 2012;7:e38766.Sonesson AK, Ødegård J, Rönnegård L. Genetic heterogeneity of within-family variance of body weight in Atlantic salmon (Salmo salar). Genet Sel Evol. 2013;45:41.Garreau H, Bolet G, Larzul C, Robert-Granie C, Saleil G, SanCristobal M, et al. Results of four generations of a canalising selection for rabbit birth weight. Livest Sci. 2008;119:55–62.Pun A, Cervantes I, Nieto B, Salgado C, Pérez-Cabal MA, Ibáñez-Escriche N, et al. 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Inhibition of Glioblastoma Growth by the Thiadiazolidinone Compound TDZD-8

This is an open-access article distributed under the terms of the Creative Commons Attribution License.[Background]: Thiadiazolidinones (TDZD) are small heterocyclic compounds first described as non-ATP competitive inhibitors of glycogen synthase kinase 3 beta (GSK-3 beta). In this study, we analyzed the effects of 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5- dione (TDZD-8), on murine GL261 cells growth in vitro and on the growth of established intracerebral murine gliomas in vivo. [Methodology/Principal Findings]: Our data show that TDZD-8 decreased proliferation and induced apoptosis of GL261 glioblastoma cells in vitro, delayed tumor growth in vivo, and augmented animal survival. These effects were associated with an early activation of extracellular signal-regulated kinase (ERK) pathway and increased expression of EGR-1 and p21 genes. Also, we observed a sustained activation of the ERK pathway, a concomitant phosphorylation and activation of ribosomal S6 kinase (p90RSK) and an inactivation of GSK-3 beta by phosphorylation at Ser 9. Finally, treatment of glioblastoma stem cells with TDZD-8 resulted in an inhibition of proliferation and self-renewal of these cells. [Conclusions/Significance]: Our results suggest that TDZD-8 uses a novel mechanism to target glioblastoma cells, and that malignant progenitor population could be a target of this compound.This work was supported by the Ministerio de Educacion y Ciencia grant SAF2007-62811 (to A.P.-C.). CIBERNED is funded by the Instituto de Salud Carlos III. JA.M.-G. and M.S.-S. are fellows of CIBERNED. D.A.-M. is a fellow of the Consejo Superior de Investigaciones Científicas.Peer reviewe

Complement component 3 (C3) expression in the hippocampus after excitotoxic injury: role of C/EBPβ

[Background] The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor implicated in the control of proliferation, differentiation, and inflammatory processes mainly in adipose tissue and liver; although more recent results have revealed an important role for this transcription factor in the brain. Previous studies from our laboratory indicated that CCAAT/enhancer-binding protein β is implicated in inflammatory process and brain injury, since mice lacking this gene were less susceptible to kainic acid-induced injury. More recently, we have shown that the complement component 3 gene (C3) is a downstream target of CCAAT/enhancer-binding protein β and it could be a mediator of the proinflammatory effects of this transcription factor in neural cells.[Methods] Adult male Wistar rats (8–12 weeks old) were used throughout the study. C/EBPβ+/+ and C/EBPβ–/– mice were generated from heterozygous breeding pairs. Animals were injected or not with kainic acid, brains removed, and brain slices containing the hippocampus analyzed for the expression of both CCAAT/enhancer-binding protein β and C3.[Results] In the present work, we have further extended these studies and show that CCAAT/enhancer-binding protein β and C3 co-express in the CA1 and CA3 regions of the hippocampus after an excitotoxic injury. Studies using CCAAT/enhancer-binding protein β knockout mice demonstrate a marked reduction in C3 expression after kainic acid injection in these animals, suggesting that indeed this protein is regulated by C/EBPβ in the hippocampus in vivo.[Conclusions] Altogether these results suggest that CCAAT/enhancer-binding protein β could regulate brain disorders, in which excitotoxic and inflammatory processes are involved, at least in part through the direct regulation of C3.This work was supported by MINECO, Grant SAF2014-52940-R and partially financed with FEDER funds. CIBERNED is funded by the Instituto de Salud Carlos III. JAM-G was supported by CIBERNED. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

Transcriptome profiling of sheep granulosa cells and oocytes during early follicular development obtained by Laser Capture Microdissection

<p>Abstract</p> <p>Background</p> <p>Successful achievement of early folliculogenesis is crucial for female reproductive function. The process is finely regulated by cell-cell interactions and by the coordinated expression of genes in both the oocyte and in granulosa cells. Despite many studies, little is known about the cell-specific gene expression driving early folliculogenesis. The very small size of these follicles and the mixture of types of follicles within the developing ovary make the experimental study of isolated follicular components very difficult.</p> <p>The recently developed laser capture microdissection (LCM) technique coupled with microarray experiments is a promising way to address the molecular profile of pure cell populations. However, one main challenge was to preserve the RNA quality during the isolation of single cells or groups of cells and also to obtain sufficient amounts of RNA.</p> <p>Using a new LCM method, we describe here the separate expression profiles of oocytes and follicular cells during the first stages of sheep folliculogenesis.</p> <p>Results</p> <p>We developed a new tissue fixation protocol ensuring efficient single cell capture and RNA integrity during the microdissection procedure. Enrichment in specific cell types was controlled by qRT-PCR analysis of known genes: six oocyte-specific genes (<it>SOHLH2</it>, <it>MAEL</it>, <it>MATER</it>, <it>VASA</it>, <it>GDF9</it>, <it>BMP15</it>) and three granulosa cell-specific genes (<it>KL</it>, <it>GATA4</it>, <it>AMH</it>).</p> <p>A global gene expression profile for each follicular compartment during early developmental stages was identified here for the first time, using a bovine Affymetrix chip. Most notably, the granulosa cell dataset is unique to date. The comparison of oocyte vs. follicular cell transcriptomes revealed 1050 transcripts specific to the granulosa cell and 759 specific to the oocyte.</p> <p>Functional analyses allowed the characterization of the three main cellular events involved in early folliculogenesis and confirmed the relevance and potential of LCM-derived RNA.</p> <p>Conclusions</p> <p>The ovary is a complex mixture of different cell types. Distinct cell populations need therefore to be analyzed for a better understanding of their potential interactions. LCM and microarray analysis allowed us to identify novel gene expression patterns in follicular cells at different stages and in oocyte populations.</p