47 research outputs found

    A shared role for RBF1 and dCAP-D3 in the regulation of transcription with consequences for innate immunity

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    Previously, we discovered a conserved interaction between RB proteins and the Condensin II protein CAP-D3 that is important for ensuring uniform chromatin condensation during mitotic prophase. The Drosophila melanogaster homologs RBF1 and dCAP-D3 co-localize on non-dividing polytene chromatin, suggesting the existence of a shared, non-mitotic role for these two proteins. Here, we show that the absence of RBF1 and dCAP-D3 alters the expression of many of the same genes in larvae and adult flies. Strikingly, most of the genes affected by the loss of RBF1 and dCAP-D3 are not classic cell cycle genes but are developmentally regulated genes with tissue-specific functions and these genes tend to be located in gene clusters. Our data reveal that RBF1 and dCAP-D3 are needed in fat body cells to activate transcription of clusters of antimicrobial peptide (AMP) genes. AMPs are important for innate immunity, and loss of either dCAP-D3 or RBF1 regulation results in a decrease in the ability to clear bacteria. Interestingly, in the adult fat body, RBF1 and dCAP-D3 bind to regions flanking an AMP gene cluster both prior to and following bacterial infection. These results describe a novel, non-mitotic role for the RBF1 and dCAP-D3 proteins in activation of the Drosophila immune system and suggest dCAP-D3 has an important role at specific subsets of RBF1-dependent genes

    Contribution of Cerebellar Sensorimotor Adaptation to Hippocampal Spatial Memory

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    Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation

    Potassium and Sodium Transport in Yeast

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    [EN] As the proper maintenance of intracellular potassium and sodium concentrations is vital for cell growth, all living organisms have developed a cohort of strategies to maintain proper monovalent cation homeostasis. In the model yeast Saccharomyces cerevisiae, potassium is accumulated to relatively high concentrations and is required for many aspects of cellular function, whereas high intracellular sodium/potassium ratios are detrimental to cell growth and survival. The fact that S. cerevisiae cells can grow in the presence of a broad range of concentrations of external potassium (10 M–2.5 M) and sodium (up to 1.5 M) indicates the existence of robust mechanisms that have evolved to maintain intracellular concentrations of these cations within appropriate limits. In this review, current knowledge regarding potassium and sodium transporters and their regulation will be summarized. The cellular responses to high sodium and potassium and potassium starvation will also be discussed, as well as applications of this knowledge to diverse fields, including antifungal treatments, bioethanol production and human disease.L.Y. is funded by grant BFU2011-30197-C03-03 from the Spanish Ministry of Science and Innovation (Madrid, Spain) and EUI2009-04147 [Systems Biology of Microorganisms (SysMo2) European Research Area-Network (ERA-NET)].Yenush, L. (2016). Potassium and Sodium Transport in Yeast. Advances in Experimental Medicine and Biology. 892:187-228. https://doi.org/10.1007/978-3-319-25304-6_8S187228892Ahmed A, Sesti F, Ilan N, Shih TM, Sturley SL et al (1999) A molecular target for viral killer toxin: TOK1 potassium channels. Cell 99:283–291Albert A, Yenush L, Gil-Mascarell MR, Rodriguez PL, Patel S et al (2000) X-ray structure of yeast Hal2p, a major target of lithium and sodium toxicity, and identification of framework interactions determining cation sensitivity. 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    Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex

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    Animal Models of Human Cerebellar Ataxias: a Cornerstone for the Therapies of the Twenty-First Century

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    Missense variants in ATM in 26,101 breast cancer cases and 29,842 controls.

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    BACKGROUND: Truncating mutations in ATM have been shown to increase the risk of breast cancer but the effect of missense variants remains contentious. METHODS: We have genotyped five polymorphic (minor allele frequency, 0.9-2.6%) missense single nucleotide polymorphisms (SNP) in ATM (S49C, S707P, F858L, P1054R, and L1420F) in 26,101 breast cancer cases and 29,842 controls from 23 studies in the Breast Cancer Association Consortium. RESULTS: Combining the data from all five SNPs, the odds ratio (OR) was 1.05 for being a heterozygote for any of the SNPs and 1.51 for being a rare homozygote for any of the SNPs with an overall trend OR of 1.06 (P(trend) = 0.04). The trend OR among bilateral and familial cases was 1.12 (95% confidence interval, 1.02-1.23; P(trend) = 0.02). CONCLUSIONS: In this large combined analysis, these five missense ATM SNPs were associated with a small increased risk of breast cancer, explaining an estimated 0.03% of the excess familial risk of breast cancer. IMPACT: Testing the combined effects of rare missense variants in known breast cancer genes in large collaborative studies should clarify their overall contribution to breast cancer susceptibility

    Cdc14 and Chromosome Condensation: Evaluation of the Recruitment of Condensin to Genomic Regions

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    Chromosome condensation is an essential morphological event required for successful DNA segregation during mitosis. The high level of genome compaction achieved during this process is attained by the evolutionary conserved condensin complex. Recently, several lines of evidences have demonstrated that the mitotic phosphatase Cdc14 is required to ensure condensin loading onto chromosomes. To date several approaches have been used in order to characterize condensin activity and regulation, however these techniques are time-consuming and require complex equipment. In this chapter we described an easy and reliable protocol to analyze Cdc14-dependent condensin loading onto specific genomic DNA regions by using a chromatin immunoprecipitation (ChIP) technique.Peer reviewe

    Viability of Biogas Production and Determination of Bacterial Kinetics in Anaerobic Co-digestion of Cabbage Waste and Livestock Manure

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    [EN] For the economically depressed communities such as of those in the Canton Guaranda, Ecuador, to generate their own energy, from organic waste is very important because they are sometimes insulated and its gas and electricity supply is very deficient. The aim of this research, was to determine the feasibility of anaerobic co-digestion of wasted cabbage from the town's market in Guaranda, Ecuador, and livestock manure. Two variables were studied: temperature of the process and the percentage of cabbage and livestock manure. Biogas quantity and kinetic parameters were evaluated. Kinetic model were analyzed by minimizing the mean percentage of error between the observed values (measured experimentally) and predicted, using the Runge-Kutta of order 4 for solving the system of differential equations obtained from mass balance. The results showed that a 50-50% ratio cabbage-manure at 30 degrees C temperature gave the highest production of biogas achieved is (389.47cm(3)N/g initial SV) with a composition of 61% methane. The kinetic parameters found were mu(max)=0.1053day(-1); Ks=0.1153mg/l; Y=0.00246g VSS /g COD and K-dec=0.001005day(-1).This research work has been carried out inside the cooperation framework funded by the ADSIDEO program of the Centro de Cooperacion al Desarrollo (CCD) of Universidad Politecnica de Valencia (Spain), in collaboration with the Centro de Estudios de la Biomasa (CEB), Universidad Estatal de Bolivar, Guaranda, Ecuador. The participation of Dr. Sergio Perez in this work was possible thanks to funding from the Ecuadorian Government by means of the PROMETEO program, led by the Secretaria Nacional de Educacion Superior, Ciencia y Tecnologia (SENESCYT).Gaibor-Chavez, J.; Niño-Ruiz, Z.; Velázquez Martí, B.; Lucio-Quintana, A. (2018). 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