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See detailAre sex drive and hypersexuality associated with pedophilic interest and child sexual abuse in a male community sample?
Klein, Verena; Schmidt, Alexander F. UL; Turner, Daniel et al

in PLoS ONE (2015), 10(7), 0129730

Although, much is currently known about hypersexuality (in form of excessive sexual behavior) among sexual offenders, the degree to which hypersexual behavior is linked to paraphilic and especially ... [more ▼]

Although, much is currently known about hypersexuality (in form of excessive sexual behavior) among sexual offenders, the degree to which hypersexual behavior is linked to paraphilic and especially pedophilic interests in non-forensic populations has not been established. The purpose of the present study was to elucidate the associations between total sexual outlets (TSO) and other sex drive indicators, antisocial behavior, pedophilic interests, and sexual offending behavior in a large population-based community sample of males. The sample included 8,718 German men who participated in an online study. Hypersexual behavior as measured by self-reported TSO, self-reported sex drive, criminal history, and pedophilic interests were assessed. In moderated hierarchical logistic regression analyses self-reported contact sexual offending against children was linked to sexual fantasizing about children and antisociality. There was no association between aggregated sex drive, and sexual abusive behaviour in the multivariate analyses. In contrast, self-reported child pornography consumption was associated with sex drive, sexual fantasies involving children, and antisociality. Nevertheless, in clinical practice an assessment of criminal history and pedophilic interests in hypersexual individuals and vice versa hypersexuality in antisocial or pedophilic men should be considered as particularly antisociality and pedophilic interest are important predictors of sexual offending against prepubescent children. [less ▲]

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See detailEffects of Endocrine Disruptor Compounds, Alone or in Combination, on Human Macrophage-Like THP-1 Cell Response
Couleau, Nicolas; Falla, Jairo; Beillerot, Adeline et al

in PLoS ONE (2015), 10(7), 0131428

The aim of the present study was to evaluate the immunological effects on human macrophages of four endocrine disruptor compounds (EDCs) using the differentiated human THP-1 cell line as a model. We ... [more ▼]

The aim of the present study was to evaluate the immunological effects on human macrophages of four endocrine disruptor compounds (EDCs) using the differentiated human THP-1 cell line as a model. We studied first the effects of these EDCs, including Bisphenol A (BPA), di-ethylhexyl-phthalate (DEHP), dibutyl phthalate (DBP) and 4-tert-octylphenol (4-OP), either alone or in combination, on cytokine secretion, and phagocytosis. We then determined whether or not these effects were mediated by estrogen receptors via MAPK pathways. It was found that all four EDCs studied reduced strongly the phagocytosis of the differentiated THP-1 cells and that several of these EDCs disturbed also TNF-α, IL-1 β and IL-8 cytokine secretions. Furthermore, relative to control treatment, decreased ERK 1/2 phosphorylation was always associated with EDCs treatments-either alone or in certain combinations (at 0.1 μM for each condition). Lastly, as treatments by an estrogen receptor antagonist suppressed the negative effects on ERK 1/2 phosphorylation observed in cells treated either alone with BPA, DEHP, 4-OP or with the combined treatment of BPA and DEHP, we suggested that estrogen receptor-dependent pathway is involved in mediating the effects of EDCs on human immune system. Altogether, these results advocate that EDCs can disturb human immune response at very low concentrations. [less ▲]

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See detailNLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes.
Gustin, Audrey; Kirchmeyer, Mélanie UL; Koncina, Eric UL et al

in PLoS ONE (2015), 10(6),

Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response ... [more ▼]

Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response involving secretion of cytokines and chemokines, resulting in the activation of astrocytes and recruitment of peripheral immune cells. IL-1β plays an important role in this response; yet its production and mode of action in the brain are not fully understood and its precise implication in neurodegenerative diseases needs further characterization. Our results indicate that the capacity to form a functional NLRP3 inflammasome and secretion of IL-1β is limited to the microglial compartment in the mouse brain. We were not able to observe IL-1β secretion from astrocytes, nor do they express all NLRP3 inflammasome components. Microglia were able to produce IL-1β in response to different classical inflammasome activators, such as ATP, Nigericin or Alum. Similarly, microglia secreted IL-18 and IL-1α, two other inflammasome-linked pro-inflammatory factors. Cell stimulation with α-synuclein, a neurodegenerative disease-related peptide, did not result in the release of active IL-1β by microglia, despite a weak pro-inflammatory effect. Amyloid-β peptides were able to activate the NLRP3 inflammasome in microglia and IL-1β secretion occurred in a P2X7 receptor-independent manner. Thus microglia-dependent inflammasome activation can play an important role in the brain and especially in neuroinflammatory conditions. [less ▲]

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See detailDiscrete Logic Modelling Optimization to Contextualize Prior Knowledge Networks Using PRUNET
Rodriguez, Ana; Crespo, Isaac UL; Androsova, Ganna UL et al

in PLoS ONE (2015), 10(6), 0127216

High-throughput technologies have led to the generation of an increasing amount of data in different areas of biology. Datasets capturing the cell’s response to its intra- and extra-cellular ... [more ▼]

High-throughput technologies have led to the generation of an increasing amount of data in different areas of biology. Datasets capturing the cell’s response to its intra- and extra-cellular microenvironment allows such data to be incorporated as signed and directed graphs or influence networks. These prior knowledge networks (PKNs) represent our current knowledge of the causality of cellular signal transduction. New signalling data is often examined and interpreted in conjunction with PKNs. However, different biological contexts, such as cell type or disease states, may have distinct variants of signalling pathways, resulting in the misinterpretation of new data. The identification of inconsistencies between measured data and signalling topologies, as well as the training of PKNs using context specific datasets (PKN contextualization), are necessary conditions to construct reliable, predictive models, which are current challenges in the systems biology of cell signalling. Here we present PRUNET, a user-friendly software tool designed to address the contextualization of a PKNs to specific experimental conditions. As the input, the algorithm takes a PKN and the expression profile of two given stable steady states or cellular phenotypes. The PKN is iteratively pruned using an evolutionary algorithm to perform an optimization process. This optimization rests in a match between predicted attractors in a discrete logic model (Boolean) and a Booleanized representation of the phenotypes, within a population of alternative subnetworks that evolves iteratively. We validated the algorithm applying PRUNET to four biological examples and using the resulting contextualized networks to predict missing expression values and to simulate well-characterized perturbations. PRUNET constitutes a tool for the automatic curation of a PKN to make it suitable for describing biological processes under particular experimental conditions. The general applicability of the implemented algorithm makes PRUNET suitable for a variety of biological processes, for instance cellular reprogramming or transitions between healthy and disease states. [less ▲]

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See detailStemness of the hybrid Epithelial/Mesenchymal State in Breast Cancer and Its Association with Poor Survival.
Grosse-Wilde, Anne; Fouquier d'Hérouël, Aymeric UL; McIntosh, Ellie et al

in PLoS ONE (2015), 10(5), 0126522

Breast cancer stem cells (CSCs) are thought to drive recurrence and metastasis. Their identity has been linked to the epithelial to mesenchymal transition (EMT) but remains highly controversial since ... [more ▼]

Breast cancer stem cells (CSCs) are thought to drive recurrence and metastasis. Their identity has been linked to the epithelial to mesenchymal transition (EMT) but remains highly controversial since-depending on the cell-line studied-either epithelial (E) or mesenchymal (M) markers, alone or together have been associated with stemness. Using distinct transcript expression signatures characterizing the three different E, M and hybrid E/M cell-types, our data support a novel model that links a mixed EM signature with stemness in 1) individual cells, 2) luminal and basal cell lines, 3) in vivo xenograft mouse models, and 4) in all breast cancer subtypes. In particular, we found that co-expression of E and M signatures was associated with poorest outcome in luminal and basal breast cancer patients as well as with enrichment for stem-like cells in both E and M breast cell-lines. This link between a mixed EM expression signature and stemness was explained by two findings: first, mixed cultures of E and M cells showed increased cooperation in mammosphere formation (indicative of stemness) compared to the more differentiated E and M cell-types. Second, single-cell qPCR analysis revealed that E and M genes could be co-expressed in the same cell. These hybrid E/M cells were generated by both E or M cells and had a combination of several stem-like traits since they displayed increased plasticity, self-renewal, mammosphere formation, and produced ALDH1+ progenies, while more differentiated M cells showed less plasticity and E cells showed less self-renewal. Thus, the hybrid E/M state reflecting stemness and its promotion by E-M cooperation offers a dual biological rationale for the robust association of the mixed EM signature with poor prognosis, independent of cellular origin. Together, our model explains previous paradoxical findings that breast CSCs appear to be M in luminal cell-lines but E in basal breast cancer cell-lines. Our results suggest that targeting E/M heterogeneity by eliminating hybrid E/M cells and cooperation between E and M cell-types could improve breast cancer patient survival independent of breast cancer-subtype. [less ▲]

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See detailProtocols and programs for high-throughput growth and aging phenotyping in yeast.
Jung, Paul UL; Christian, Nils UL; Kay, Daniel UL et al

in PloS one (2015), 10(3), 0119807

In microorganisms, and more particularly in yeasts, a standard phenotyping approach consists in the analysis of fitness by growth rate determination in different conditions. One growth assay that combines ... [more ▼]

In microorganisms, and more particularly in yeasts, a standard phenotyping approach consists in the analysis of fitness by growth rate determination in different conditions. One growth assay that combines high throughput with high resolution involves the generation of growth curves from 96-well plate microcultivations in thermostated and shaking plate readers. To push the throughput of this method to the next level, we have adapted it in this study to the use of 384-well plates. The values of the extracted growth parameters (lag time, doubling time and yield of biomass) correlated well between experiments carried out in 384-well plates as compared to 96-well plates or batch cultures, validating the higher-throughput approach for phenotypic screens. The method is not restricted to the use of the budding yeast Saccharomyces cerevisiae, as shown by consistent results for other species selected from the Hemiascomycete class. Furthermore, we used the 384-well plate microcultivations to develop and validate a higher-throughput assay for yeast Chronological Life Span (CLS), a parameter that is still commonly determined by a cumbersome method based on counting "Colony Forming Units". To accelerate analysis of the large datasets generated by the described growth and aging assays, we developed the freely available software tools GATHODE and CATHODE. These tools allow for semi-automatic determination of growth parameters and CLS behavior from typical plate reader output files. The described protocols and programs will increase the time- and cost-efficiency of a number of yeast-based systems genetics experiments as well as various types of screens. [less ▲]

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See detailPharmacological characterization of an antisense knockdown zebrafish model of Dravet syndrome: Inhibition of epileptic seizures by the serotonin agonist fenfluramine
Zhang, Yang UL; Kecskés, A.; Copmans, D. et al

in PLoS ONE (2015), 10(5),

Dravet syndrome (DS) is one of the most pharmacoresistant and devastating forms of childhood epilepsy syndromes. Distinct de novo mutations in the SCN1A gene are responsible for over 80% of DS cases ... [more ▼]

Dravet syndrome (DS) is one of the most pharmacoresistant and devastating forms of childhood epilepsy syndromes. Distinct de novo mutations in the SCN1A gene are responsible for over 80% of DS cases. While DS is largely resistant to treatment with existing anti-epileptic drugs, promising results have been obtained in clinical trials with human patients treated with the serotonin agonist fenfluramine as an add-on therapeutic. We developed a zebrafish model of DS using morpholino antisense oligomers (MOs) targeting scn1Lab, the zebrafish ortholog of SCN1A. Zebrafish larvae with an antisense knockdown of scn1Lab (scn1Lab morphants) were characterized by automated behavioral tracking and high-resolution video imaging, in addition to measuring brain activity through local field potential recordings. Our findings reveal that scn1Lab morphants display hyperactivity, convulsive seizure-like behavior, loss of posture, repetitive jerking and a myoclonic seizure-like pattern. The occurrence of spontaneous seizures was confirmed by local field potential recordings of the forebrain, measuring epileptiform discharges. Furthermore, we show that these larvae are remarkably sensitive to hyperthermia, similar to what has been described for mouse models of DS, as well as for human DS patients. Pharmacological evaluation revealed that sodium valproate and fenfluramine significantly reduce epileptiform discharges in scn1Lab morphants. Our findings for this zebrafish model of DS are in accordance with clinical data for human DS patients. To our knowledge, this is the first study demonstrating effective seizure inhibition of fenfluramine in an animal model of Dravet syndrome. Moreover, these results provide a basis for identifying novel analogs with improved activity and significantly milder or no side effects. © 2015 Zhang et al. [less ▲]

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See detailA social gradient in fatal opioids and cocaine related overdoses?
Origer, Alain; Le Bihan, Etienne UL; Baumann, Michèle UL

in PLoS ONE (2015), 4(10(5)),

To determine the existence of a social gradient in fatal overdose cases related to non-prescribed opioids and cocaine use, recorded in Luxembourg between 1994 and 2011. METHODS: Overdose cases were ... [more ▼]

To determine the existence of a social gradient in fatal overdose cases related to non-prescribed opioids and cocaine use, recorded in Luxembourg between 1994 and 2011. METHODS: Overdose cases were individually matched with four controls in a nested case-control study design, according to sex, year of birth, drug administration route and duration of drug use. The study sample, composed of 272 cases and 1,056 controls, was stratified according to a Social Inequality Accumulation Score (SIAS), based on educational attainment, employment, income, financial situation of subjects and the professional status of their father or legal guardian. Least squares linear regression analysis on overdose mortality rates and ridit scores were applied to determine the Relative Index of Inequality (RII) of the study sample. RESULTS: A negative linear relationship between the overdose mortality rate and the relative socioeconomic position was observed. We found a difference in mortality of 29.22 overdose deaths per 100 drug users in the lowest socioeconomic group compared to the most advantaged group. In terms of the Relative Inequality Index, the overdose mortality rate of opioid and cocaine users with lowest socioeconomic profiles was 9.88 times as high as that of their peers from the highest socioeconomic group (95% CI 6.49-13.26). CONCLUSIONS: Our findings suggest the existence of a marked social gradient in opioids and cocaine related overdose fatalities. Harm reduction services should integrate socially supportive offers, not only because of their general aim of social (re)integration but crucially in order to meet their most important objective, that is to reduce drug-related mortality [less ▲]

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See detailSelectivity of Face Perception to Horizontal Information over Lifespan (from 6 to 74 Year Old).
Goffaux, Valerie; Poncin, Aude; Schiltz, Christine UL

in PloS one (2015), 10(9), 0138812

Face recognition in young human adults preferentially relies on the processing of horizontally-oriented visual information. We addressed whether the horizontal tuning of face perception is modulated by ... [more ▼]

Face recognition in young human adults preferentially relies on the processing of horizontally-oriented visual information. We addressed whether the horizontal tuning of face perception is modulated by the extensive experience humans acquire with faces over the lifespan, or whether it reflects an invariable processing bias for this visual category. We tested 296 subjects aged from 6 to 74 years in a face matching task. Stimuli were upright and inverted faces filtered to preserve information in the horizontal or vertical orientation, or both (HV) ranges. The reliance on face-specific processing was inferred based on the face inversion effect (FIE). FIE size increased linearly until young adulthood in the horizontal but not the vertical orientation range of face information. These findings indicate that the protracted specialization of the face processing system relies on the extensive experience humans acquire at encoding the horizontal information conveyed by upright faces. [less ▲]

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See detailThe European general practice research network presents the translations of its comprehensive definition of multimorbidity in family medicine in ten European languages.
Le Reste, Jean Yves; Nabbe, Patrice; Rivet, Charles et al

in PloS one (2015), 10(1), 0115796

BACKGROUND: Multimorbidity, according to the World Health Organization, exists when there are two or more chronic conditions in one patient. This definition seems inaccurate for the holistic approach to ... [more ▼]

BACKGROUND: Multimorbidity, according to the World Health Organization, exists when there are two or more chronic conditions in one patient. This definition seems inaccurate for the holistic approach to Family Medicine (FM) and long-term care. To avoid this pitfall the European General Practitioners Research Network (EGPRN) designed a comprehensive definition of multimorbidity using a systematic literature review. OBJECTIVE: To translate that English definition into European languages and to validate the semantic, conceptual and cultural homogeneity of the translations for further research. METHOD: Forward translation of the EGPRN's definition of multimorbidity followed by a Delphi consensus procedure assessment, a backward translation and a cultural check with all teams to ensure the homogeneity of the translations in their national context. Consensus was defined as 70% of the scores being higher than 6. Delphi rounds were repeated in each country until a consensus was reached. RESULTS: 229 European medical expert FPs participated in the study. Ten consensual translations of the EGPRN comprehensive definition of multimorbidity were achieved. CONCLUSION: A comprehensive definition of multimorbidity is now available in English and ten European languages for further collaborative research in FM and long-term care. [less ▲]

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See detailThe NG2 Proteoglycan Protects Oligodendrocyte Precursor Cells against Oxidative Stress via Interaction with OMI/HtrA2
Maus, F.; Sakry, D.; Biname, F. et al

in PLoS ONE (2015), 10(9), 0137311

The NG2 proteoglycan is characteristically expressed by oligodendrocyte progenitor cells (OPC) and also by aggressive brain tumours highly resistant to chemo- and radiation therapy. Oligodendrocyte ... [more ▼]

The NG2 proteoglycan is characteristically expressed by oligodendrocyte progenitor cells (OPC) and also by aggressive brain tumours highly resistant to chemo- and radiation therapy. Oligodendrocyte-lineage cells are particularly sensitive to stress resulting in cell death in white matter after hypoxic or ischemic insults of premature infants and destruction of OPC in some types of Multiple Sclerosis lesions. Here we show that the NG2 proteoglycan binds OMI/HtrA2, a mitochondrial serine protease which is released from damaged mitochondria into the cytosol in response to stress. In the cytosol, OMI/HtrA2 initiates apoptosis by proteolytic degradation of anti-apoptotic factors. OPC in which NG2 has been downregulated by siRNA, or OPC from the NG2-knockout mouse show an increased sensitivity to oxidative stress evidenced by increased cell death. The proapoptotic protease activity of OMI/HtrA2 in the cytosol can be reduced by the interaction with NG2. Human glioma expressing high levels of NG2 are less sensitive to oxidative stress than those with lower NG2 expression and reducing NG2 expression by siRNA increases cell death in response to oxidative stress. Binding of NG2 to OMI/HtrA2 may thus help protect cells against oxidative stress-induced cell death. This interaction is likely to contribute to the high chemo- and radioresistance of glioma. [less ▲]

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See detailMediaDB: A Database of Microbial Growth Conditions in Defined Media
Richards, Matthew A.; Cassen, Victor; Heavner, Benjamin D. et al

in PLoS ONE (2014), 9(8), 103548

Isolating pure microbial cultures and cultivating them in the laboratory on defined media is used to more fully characterize the metabolism and physiology of organisms. However, identifying an appropriate ... [more ▼]

Isolating pure microbial cultures and cultivating them in the laboratory on defined media is used to more fully characterize the metabolism and physiology of organisms. However, identifying an appropriate growth medium for a novel isolate remains a challenging task. Even organisms with sequenced and annotated genomes can be difficult to grow, despite our ability to build genome-scale metabolic networks that connect genomic data with metabolic function. The scientific literature is scattered with information about defined growth media used successfully for cultivating a wide variety of organisms, but to date there exists no centralized repository to inform efforts to cultivate less characterized organisms by bridging the gap between genomic data and compound composition for growth media. Here we present MediaDB, a manually curated database of defined media that have been used for cultivating organisms with sequenced genomes, with an emphasis on organisms with metabolic network models. The database is accessible online, can be queried by keyword searches or downloaded in its entirety, and can generate exportable individual media formulation files. The data assembled in MediaDB facilitate comparative studies of organism growth media, serve as a starting point for formulating novel growth media, and contribute to formulating media for in silico investigation of metabolic networks. MediaDB is freely available for public use at https://mediadb.systemsbiology.net. [less ▲]

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See detailoptPBN: An Optimisation Toolbox for Probabilistic Boolean Networks
Trairatphisan, Panuwat UL; Mizera, Andrzej UL; Pang, Jun UL et al

in PLoS ONE (2014), 9(7), 980011-15

Background There exist several computational tools which allow for the optimisation and inference of biological networks using a Boolean formalism. Nevertheless, the results from such tools yield only ... [more ▼]

Background There exist several computational tools which allow for the optimisation and inference of biological networks using a Boolean formalism. Nevertheless, the results from such tools yield only limited quantitative insights into the complexity of biological systems because of the inherited qualitative nature of Boolean networks. Results We introduce optPBN, a Matlab-based toolbox for the optimisation of probabilistic Boolean networks (PBN) which operates under the framework of the BN/PBN toolbox. optPBN offers an easy generation of probabilistic Boolean networks from rule-based Boolean model specification and it allows for flexible measurement data integration from multiple experiments. Subsequently, optPBN generates integrated optimisation problems which can be solved by various optimisers. In term of functionalities, optPBN allows for the construction of a probabilistic Boolean network from a given set of potential constitutive Boolean networks by optimising the selection probabilities for these networks so that the resulting PBN fits experimental data. Furthermore, the optPBN pipeline can also be operated on large-scale computational platforms to solve complex optimisation problems. Apart from exemplary case studies which we correctly inferred the original network, we also successfully applied optPBN to study a large-scale Boolean model of apoptosis where it allows identifying the inverse correlation between UVB irradiation, NFκB and Caspase 3 activations, and apoptosis in primary hepatocytes quantitatively. Also, the results from optPBN help elucidating the relevancy of crosstalk interactions in the apoptotic network. Summary The optPBN toolbox provides a simple yet comprehensive pipeline for integrated optimisation problem generation in the PBN formalism that can readily be solved by various optimisers on local or grid-based computational platforms. optPBN can be further applied to various biological studies such as the inference of gene regulatory networks or the identification of the interaction's relevancy in signal transduction networks. [less ▲]

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See detailEffect of seated trunk posture on eye blink startle and subjective experience: Comparing flexion, neutral upright posture, and extension of spine
Ceunen, Erik UL; Zaman, Jonas; Vlaeyen, Johan et al

in PLoS ONE (2014), 9(2),

Postures are known to be able to affect emotion and motivation. Much less is known about whether (affective) modulation of eye blink startle occurs following specific postures. The objective of the ... [more ▼]

Postures are known to be able to affect emotion and motivation. Much less is known about whether (affective) modulation of eye blink startle occurs following specific postures. The objective of the current study was to explore this. Participants in the present study were requested to assume three different sitting postures: with the spine flexed (slouched), neutral upright, and extended. Each posture was assumed for four minutes, and was followed by the administration of brief self-report questionnaires before proceeding to the next posture. The same series of postures and measures were repeated prior to ending the experiment. Results indicate that, relative to the other postures, the extended sitting posture was associated with an increased startle, was more unpleasant, arousing, had smaller levels of dominance, induced more discomfort, and was perceived as more difficult. The upright and flexed sitting postures differed in the level of self-reported positive affect, but not in eye blink startle amplitudes. [less ▲]

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See detailThe Impact of Mathematical Proficiency on the Number-Space Association
Hoffmann, Danielle UL; Mussolin, Christophe; Martin, Romain UL et al

in PLoS ONE (2014)

A specific instance of the association between numerical and spatial representations is the SNARC (Spatial Numerical Association of Response Codes) effect. The SNARC effect describes the finding that ... [more ▼]

A specific instance of the association between numerical and spatial representations is the SNARC (Spatial Numerical Association of Response Codes) effect. The SNARC effect describes the finding that during binary classification of numbers participants are faster to respond to small/large numbers with the left/right hand respectively. Even though it has been frequently replicated, important inter-individual variability has also been reported. Mathematical proficiency is an obvious candidate source for inter-individual variability in numerical judgments, but studies investigating its influence on the SNARC effect remain scarce. The present experiment included a total of 95 University students, divided into three groups differing significantly in their mathematical proficiency levels. Using group analyses, it appeared that the three groups differed significantly in the strength of their number-space associations in a parity judgment task. This result was further confirmed on an individual level, with higher levels in arithmetic leading to relatively weaker SNARC effects. To explain this negative relationship we propose accounts based on differences in access to qualitatively different numerical representations and also consider more domain general factors, with a focus on inhibition capacities. [less ▲]

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See detailDiscovering pair-wise genetic interactions: an information theory-based approach.
Ignac, Tomasz UL; Skupin, Alexander UL; Sakhanenko, Nikita A. et al

in PloS one (2014), 9(3), 92310

Phenotypic variation, including that which underlies health and disease in humans, results in part from multiple interactions among both genetic variation and environmental factors. While diseases or ... [more ▼]

Phenotypic variation, including that which underlies health and disease in humans, results in part from multiple interactions among both genetic variation and environmental factors. While diseases or phenotypes caused by single gene variants can be identified by established association methods and family-based approaches, complex phenotypic traits resulting from multi-gene interactions remain very difficult to characterize. Here we describe a new method based on information theory, and demonstrate how it improves on previous approaches to identifying genetic interactions, including both synthetic and modifier kinds of interactions. We apply our measure, called interaction distance, to previously analyzed data sets of yeast sporulation efficiency, lipid related mouse data and several human disease models to characterize the method. We show how the interaction distance can reveal novel gene interaction candidates in experimental and simulated data sets, and outperforms other measures in several circumstances. The method also allows us to optimize case/control sample composition for clinical studies. [less ▲]

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See detailSystematic Design of 18S rRNA Gene Primers for Determining Eukaryotic Diversity in Microbial Consortia
Hugerth, Luisa; Muller, Emilie UL; Hu, Yue et al

in PLoS ONE (2014)

High-throughput sequencing of ribosomal RNA gene (rDNA) amplicons has opened up the door to large-scale comparative studies of microbial community structures. The short reads currently produced by ... [more ▼]

High-throughput sequencing of ribosomal RNA gene (rDNA) amplicons has opened up the door to large-scale comparative studies of microbial community structures. The short reads currently produced by massively parallel sequencing technologies make the choice of sequencing region crucial for accurate phylogenetic assignments. While for 16S rDNA, relevant regions have been well described, no truly systematic design of 18S rDNA primers aimed at resolving eukaryotic diversity has yet been reported. Here we used 31,862 18S rDNA sequences to design a set of broad-taxonomic range degenerate PCR primers. We simulated the phylogenetic information that each candidate primer pair would retrieve using paired- or single-end reads of various lengths, representing different sequencing technologies. Primer pairs targeting the V4 region performed best, allowing discrimination with paired-end reads as short as 150 bp (with 75% accuracy at genus level). The conditions for PCR amplification were optimised for one of these primer pairs and this was used to amplify 18S rDNA sequences from isolates as well as from a range of environmental samples which were then Illumina sequenced and analysed, revealing good concordance between expected and observed results. In summary, the reported primer sets will allow minimally biased assessment of eukaryotic diversity in different microbial ecosystems. [less ▲]

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See detailElevated social stress levels and depressive symptoms in primary hyperhidrosis
Gross, K. M.; Schote, A. B.; Schneider, K. K. et al

in PLoS ONE (2014), 9(3), 92412

Detailed reference viewed: 149 (2 UL)