142 research outputs found

    Models of Star-Planet Magnetic Interaction

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    Magnetic interactions between a planet and its environment are known to lead to phenomena such as aurorae and shocks in the solar system. The large number of close-in exoplanets that were discovered triggered a renewed interest in magnetic interactions in star-planet systems. Multiple other magnetic effects were then unveiled, such as planet inflation or heating, planet migration, planetary material escape, and even modification of the host star properties. We review here the recent efforts in modelling and understanding magnetic interactions between stars and planets in the context of compact systems. We first provide simple estimates of the effects of magnetic interactions and then detail analytical and numerical models for different representative scenarii. We finally lay out a series of future developments that are needed today to better understand and constrain these fascinating interactions.Comment: 23 pages, 10 figures, accepted as a chapter in the Handbook of Exoplanet

    Genetic Analysis of Human Traits In Vitro: Drug Response and Gene Expression in Lymphoblastoid Cell Lines

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    Lymphoblastoid cell lines (LCLs), originally collected as renewable sources of DNA, are now being used as a model system to study genotype–phenotype relationships in human cells, including searches for QTLs influencing levels of individual mRNAs and responses to drugs and radiation. In the course of attempting to map genes for drug response using 269 LCLs from the International HapMap Project, we evaluated the extent to which biological noise and non-genetic confounders contribute to trait variability in LCLs. While drug responses could be technically well measured on a given day, we observed significant day-to-day variability and substantial correlation to non-genetic confounders, such as baseline growth rates and metabolic state in culture. After correcting for these confounders, we were unable to detect any QTLs with genome-wide significance for drug response. A much higher proportion of variance in mRNA levels may be attributed to non-genetic factors (intra-individual variance—i.e., biological noise, levels of the EBV virus used to transform the cells, ATP levels) than to detectable eQTLs. Finally, in an attempt to improve power, we focused analysis on those genes that had both detectable eQTLs and correlation to drug response; we were unable to detect evidence that eQTL SNPs are convincingly associated with drug response in the model. While LCLs are a promising model for pharmacogenetic experiments, biological noise and in vitro artifacts may reduce power and have the potential to create spurious association due to confounding

    Assessment of Metabolic Phenotypes in Patients with Non-ischemic Dilated Cardiomyopathy Undergoing Cardiac Resynchronization Therapy

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    Studies of myocardial metabolism have reported that contractile performance at a given myocardial oxygen consumption (MVO2) can be lower when the heart is oxidizing fatty acids rather than glucose or lactate. The objective of this study is to assess the prognostic value of myocardial metabolic phenotypes in identifying non-responders among non-ischemic dilated cardiomyopathy (NIDCM) patients undergoing cardiac resynchronization therapy (CRT). Arterial and coronary sinus plasma concentrations of oxygen, glucose, lactate, pyruvate, free fatty acids (FFA), and 22 amino acids were obtained from 19 male and 2 female patients (mean age 56 ± 16) with NIDCM undergoing CRT. Metabolite fluxes/MVO2 and extraction fractions were calculated. Flux balance analysis (FBA) was performed with MetaFluxNet 1.8 on a metabolic network of the cardiac mitochondria (189 reactions, 230 metabolites) reconstructed from mitochondrial proteomic data (615 proteins) from human heart tissue. Non-responders based on left ventricular ejection fraction (LVEF) demonstrated a greater mean FFA extraction fraction (35% ± 17%) than responders [18 ± 10%, p = 0.0098, area under the estimated ROC curve (AUC) was 0.8238, S.E. 0.1115]. Calculated adenosine triphosphate (ATP)/MVO2 using FBA correlated with change in New York Heart Association (NYHA) class (rho = 0.63, p = 0.0298; AUC = 0.8381, S.E. 0.1316). Non-responders based on both LVEF and NYHA demonstrated a greater mean FFA uptake/MVO2 (0.115 ± 0.112) than responders (0.034 ± 0.030, p = 0.0171; AUC = 0.8593, S.E. 0.0965). Myocardial FFA flux and calculated maximal ATP synthesis flux using FBA may be helpful as biomarkers in identifying non-responders among NIDCM patients undergoing CRT

    Genome-wide expression quantitative trait loci (eQTL) analysis in maize

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    <p>Abstract</p> <p>Background</p> <p>Expression QTL analyses have shed light on transcriptional regulation in numerous species of plants, animals, and yeasts. These microarray-based analyses identify regulators of gene expression as either cis-acting factors that regulate proximal genes, or trans-acting factors that function through a variety of mechanisms to affect transcript abundance of unlinked genes.</p> <p>Results</p> <p>A hydroponics-based genetical genomics study in roots of a <it>Zea mays </it>IBM2 Syn10 double haploid population identified tens of thousands of cis-acting and trans-acting eQTL. Cases of false-positive eQTL, which results from the lack of complete genomic sequences from both parental genomes, were described. A candidate gene for a trans-acting regulatory factor was identified through positional cloning. The unexpected regulatory function of a class I glutamine amidotransferase controls the expression of an ABA 8'-hydroxylase pseudogene.</p> <p>Conclusions</p> <p>Identification of a candidate gene underlying a trans-eQTL demonstrated the feasibility of eQTL cloning in maize and could help to understand the mechanism of gene expression regulation. Lack of complete genome sequences from both parents could cause the identification of false-positive cis- and trans-acting eQTL.</p

    An Analysis of the Myocardial Transcriptome in a Mouse Model of Cardiac Dysfunction with Decreased Cholinergic Neurotransmission

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    Autonomic dysfunction is observed in many cardiovascular diseases and contributes to cardiac remodeling and heart disease. We previously reported that a decrease in the expression levels of the vesicular acetylcholine transporter (VAChT) in genetically-modified homozygous mice (VAChT KDHOM) leads to decreased cholinergic tone, autonomic imbalance and a phenotype resembling cardiac dysfunction. In order to further understand the molecular changes resulting from chronic long-term decrease in parasympathetic tone, we undertook a transcriptome-based, microarray-driven approach to analyze gene expression changes in ventricular tissue from VAChT KDHOM mice. We demonstrate that a decrease in cholinergic tone is associated with alterations in gene expression in mutant hearts, which might contribute to increased ROS levels observed in these cardiomyocytes. In contrast, in another model of cardiac remodeling and autonomic imbalance, induced through chronic isoproterenol treatment to increase sympathetic drive, these genes did not appear to be altered in a pattern similar to that observed in VAChT KDHOM hearts. These data suggest the importance of maintaining a fine balance between the two branches of the autonomic nervous system and the significance of absolute levels of cholinergic tone in proper cardiac function

    The Annotation, Mapping, Expression and Network (AMEN) suite of tools for molecular systems biology

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    <p>Abstract</p> <p>Background</p> <p>High-throughput genome biological experiments yield large and multifaceted datasets that require flexible and user-friendly analysis tools to facilitate their interpretation by life scientists. Many solutions currently exist, but they are often limited to specific steps in the complex process of data management and analysis and some require extensive informatics skills to be installed and run efficiently.</p> <p>Results</p> <p>We developed the Annotation, Mapping, Expression and Network (AMEN) software as a stand-alone, unified suite of tools that enables biological and medical researchers with basic bioinformatics training to manage and explore genome annotation, chromosomal mapping, protein-protein interaction, expression profiling and proteomics data. The current version provides modules for (i) uploading and pre-processing data from microarray expression profiling experiments, (ii) detecting groups of significantly co-expressed genes, and (iii) searching for enrichment of functional annotations within those groups. Moreover, the user interface is designed to simultaneously visualize several types of data such as protein-protein interaction networks in conjunction with expression profiles and cellular co-localization patterns. We have successfully applied the program to interpret expression profiling data from budding yeast, rodents and human.</p> <p>Conclusion</p> <p>AMEN is an innovative solution for molecular systems biological data analysis freely available under the GNU license. The program is available via a website at the Sourceforge portal which includes a user guide with concrete examples, links to external databases and helpful comments to implement additional functionalities. We emphasize that AMEN will continue to be developed and maintained by our laboratory because it has proven to be extremely useful for our genome biological research program.</p

    Genes Differentially Expressed in Conidia and Hyphae of Aspergillus fumigatus upon Exposure to Human Neutrophils

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    Aspergillus fumigatus is the most common etiologic agent of invasive aspergillosis in immunocompromised patients. Several studies have addressed the mechanism involved in host defense but only few have investigated the pathogen's response to attack by the host cells. To our knowledge, this is the first study that investigates the genes differentially expressed in conidia vs hyphae of A. fumigatus in response to neutrophils from healthy donors as well as from those with chronic granulomatous disease (CGD) which are defective in the production of reactive oxygen species.Transcriptional profiles of conidia and hyphae exposed to neutrophils, either from normal donors or from CGD patients, were obtained by using the genome-wide microarray. Upon exposure to either normal or CGD neutrophils, 244 genes were up-regulated in conidia but not in hyphae. Several of these genes are involved in the degradation of fatty acids, peroxisome function and the glyoxylate cycle which suggests that conidia exposed to neutrophils reprogram their metabolism to adjust to the host environment. In addition, the mRNA levels of four genes encoding proteins putatively involved in iron/copper assimilation were found to be higher in conidia and hyphae exposed to normal neutrophils compared to those exposed to CGD neutrophils. Deletants in several of the differentially expressed genes showed phenotypes related to the proposed functions, i.e. deletants of genes involved in fatty acid catabolism showed defective growth on fatty acids and the deletants of iron/copper assimilation showed higher sensitivity to the oxidative agent menadione. None of these deletants, however, showed reduced resistance to neutrophil attack.This work reveals the complex response of the fungus to leukocytes, one of the major host factors involved in antifungal defense, and identifies fungal genes that may be involved in establishing or prolonging infections in humans

    Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

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    <p>Abstract</p> <p>Background</p> <p>Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients.</p> <p>Methods</p> <p>In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPα and sAPPβ), amyloid beta fragment 1-42 (Aβ<sub>1-42</sub>), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease.</p> <p>Results</p> <p>CSF sAPPα and sAPPβ concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Aβ<sub>1-42 </sub>in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections.</p> <p>Conclusions</p> <p>Parallel reductions of CSF sAPPα and sAPPβ in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.</p

    Conjectures on exact solution of three - dimensional (3D) simple orthorhombic Ising lattices

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    We report the conjectures on the three-dimensional (3D) Ising model on simple orthorhombic lattices, together with the details of calculations for a putative exact solution. Two conjectures, an additional rotation in the fourth curled-up dimension and the weight factors on the eigenvectors, are proposed to serve as a boundary condition to deal with the topologic problem of the 3D Ising model. The partition function of the 3D simple orthorhombic Ising model is evaluated by spinor analysis, by employing these conjectures. Based on the validity of the conjectures, the critical temperature of the simple orthorhombic Ising lattices could be determined by the relation of KK* = KK' + KK'' + K'K'' or sinh 2K sinh 2(K' + K'' + K'K''/K) = 1. For a simple cubic Ising lattice, the critical point is putatively determined to locate exactly at the golden ratio xc = exp(-2Kc) = (sq(5) - 1)/2, as derived from K* = 3K or sinh 2K sinh 6K = 1. If the conjectures would be true, the specific heat of the simple orthorhombic Ising system would show a logarithmic singularity at the critical point of the phase transition. The spontaneous magnetization and the spin correlation functions of the simple orthorhombic Ising ferromagnet are derived explicitly. The putative critical exponents derived explicitly for the simple orthorhombic Ising lattices are alpha = 0, beta = 3/8, gamma = 5/4, delta = 13/3, eta = 1/8 and nu = 2/3, showing the universality behavior and satisfying the scaling laws. The cooperative phenomena near the critical point are studied and the results obtained based on the conjectures are compared with those of the approximation methods and the experimental findings. The 3D to 2D crossover phenomenon differs with the 2D to 1D crossover phenomenon and there is a gradual crossover of the exponents from the 3D values to the 2D ones.Comment: 176 pages, 4 figure
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