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See detailThe provision of urban green space and its accessibility: Spatial data effects in Brussels
Le Texier, Marion UL; Schiel, Kerry UL; Caruso, Geoffrey UL

in PLoS ONE (2018), 13(10), 0204684

Urban green space (UGS) has many environmental and social benefits. UGS provision and access are increasingly considered in urban policies and must rely on data and indicators that can capture variations ... [more ▼]

Urban green space (UGS) has many environmental and social benefits. UGS provision and access are increasingly considered in urban policies and must rely on data and indicators that can capture variations in the distribution of UGS within cities. There is no consensus about how UGS, and their provision and access, must be defined from different land use data types. Here we identify four spatial dimensions of UGS and critically examine how different data sources affect these dimensions and our understanding of their variation within a city region (Brussels). We compare UGS indicators measured from an imagery source (NDVI from Landsat), an official cadastre-based map, and the voluntary geographical information provided by OpenStreetMap (OSM). We compare aggregate values of provision and access to UGS as well as their spatial distribution along a centrality gradient and at neighbourhood scale. We find that there are strong differences in the value of indicators when using the different datasets, especially due to their ability to capture private and public green space. However we find that the interpretation of intra-urban spatial variations is not affected by changes in data source. Centrality in particular is a strong determinant of the relative values of UGS availability, fragmentation and accessibility, irrespective of datasets. [less ▲]

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See detailRare gene deletions in genetic generalized and Rolandic epilepsies
Jabbari, Kamel; Bobbili, Dheeraj Reddy UL; Lal, Dennis et al

in PLoS ONE (2018)

Genetic Generalized Epilepsy (GGE) and benign epilepsy with centro-temporal spikes or Rolandic Epilepsy (RE) are common forms of genetic epilepsies. Rare copy number variants have been recognized as ... [more ▼]

Genetic Generalized Epilepsy (GGE) and benign epilepsy with centro-temporal spikes or Rolandic Epilepsy (RE) are common forms of genetic epilepsies. Rare copy number variants have been recognized as important risk factors in brain disorders. We performed a systematic survey of rare deletions affecting protein-coding genes derived from exome data of patients with common forms of genetic epilepsies. We analysed exomes from 390 European patients (196 GGE and 194 RE) and 572 population controls to identify low-frequency genic deletions. We found that 75 (32 GGE and 43 RE) patients out of 390, i.e. ~19%, carried rare genic deletions. In particular, large deletions (>400 kb) represent a higher burden in both GGE and RE syndromes as compared to controls. The detected low-frequency deletions (1) share genes with brain-expressed exons that are under negative selection, (2) overlap with known autism and epilepsy-associated candidate genes, (3) are enriched for CNV intolerant genes recorded by the Exome Aggregation Consortium (ExAC) and (4) coincide with likely disruptive de novo mutations from the NPdenovo database. Employing several knowledge databases, we discuss the most prominent epilepsy candidate genes and their protein-protein networks for GGE and RE. [less ▲]

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See detailDoes attention bias modification training impact on task performance in the context of pain: An experimental study in healthy participants
Van Ryckeghem, Dimitri UL; Van Damme, Stefaan; Vervoort, Tine

in PLoS ONE (2018)

Attention has been theorized to play a key role in the experience of pain and associated task interference. Training attention away from pain via attention bias modification (ABM) training techniques has ... [more ▼]

Attention has been theorized to play a key role in the experience of pain and associated task interference. Training attention away from pain via attention bias modification (ABM) training techniques has been proposed to improve pain-related outcomes, but evidence is inconsistent. In an experimental study, we investigated the impact of a single session ABM training -using a visual probe paradigm with idiosyncratic pain words- on cold pressor test (CPT) pain experience and task interference by pain. Fifty-eight healthy volunteers were randomly assigned to an ABM training group (N = 28; attending away from pain) and a sham training group (N = 30; no training direction). At pre-training, participants performed a baseline Random-Interval-Repetition (RIR) task and the CPT. Participants reported on sensations they experienced during the baseline CPT. Relevant descriptors were integrated in the visual probe paradigm during the training phase. At post-training, participants completed the RIR task again while experiencing CPT pain. Participants also reported on the extent they attended to the pain and the intensity/unpleasantness of the pain. Results indicated that, in contrast with our hypotheses, ABM training did also not reduce task interference due to CPT pain. Furthermore, ABM training did not change self-reported attending to CPT pain. Finally, ABM training did not reduce CPT pain intensity or pain unpleasantness. Overall, the current study provides no support for the effectiveness of a single session ABM training in improving pain-related outcomes. Future research addressing the conditions under which ABM training improves or fails to improve pain-related outcomes is warranted. [less ▲]

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See detailPsychological, cognitive factors and contextual influences in pain and pain-related suffering as revealed by a combined qualitative and quantitative assessment approach
Bustan S; Gonzalez-Roldan AM; Schommer, Christoph UL et al

in PLoS ONE (2018)

Previous psychophysiological research suggests that pain measurement needs to go beyond the assessment of Pain Intensity and Unpleasantness by adding the evaluation of Pain-Related Suffering. Based on ... [more ▼]

Previous psychophysiological research suggests that pain measurement needs to go beyond the assessment of Pain Intensity and Unpleasantness by adding the evaluation of Pain-Related Suffering. Based on this three-dimensional approach, we attempted to elucidate who is more likely to suffer by identifying reasons that may lead individuals to report Pain and Pain-Related Suffering more than others. A sample of 24 healthy participants (age range 18±33) underwent four different sessions involving the evaluation of experimentally induced phasic and tonic pain. We applied two decision tree models to identify variables (selected from psychological questionnaires regarding pain and descriptors from post-session interviews) that provided a qualitative characterization of the degrees of Pain Intensity, Unpleasantness and Suffering and assessed the respective impact of contextual influences. The overall classification accuracy of the decision trees was 75% for Intensity, 77% for Unpleasantness and 78% for Pain-Related Suffering. The reporting of suffering was predominantly associated with fear of pain and active cognitive coping strategies, pain intensity with bodily competence conveying strength and resistance and unpleasantness with the degree of fear of pain and catastrophizing. These results indicate that the appraisal of the three pain dimensions was largely determined by stable psychological constructs. They also suggest that individuals manifesting higher active coping strategies may suffer less despite enhanced pain and those who fear pain may suffer even under low pain. The second decision tree model revealed that suffering did not depend on pain alone, but that the complex rating-related decision making can be shifted by situational factors (context, emotional and cognitive). The impact of coping and fear of pain on individual Pain-Related Suffering may highlight the importance of improving cognitive coping strategies in clinical settings. [less ▲]

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See detailAutomatic social comparison: Cognitive load facilitates an increase in negative thought accessibility after thin ideal exposure among women
Bocage-Barthélémy, Yvana; Chatard, Armand; Jaafari, Nematollah et al

in PLoS ONE (2018), 13(3), 0193200

Women are routinely exposed to images of extremely slim female bodies (the thin ideal) in advertisements, even if they do not necessarily pay much attention to these images. We hypothesized that ... [more ▼]

Women are routinely exposed to images of extremely slim female bodies (the thin ideal) in advertisements, even if they do not necessarily pay much attention to these images. We hypothesized that paradoxically, it is precisely in such conditions of low attention that the impact of the social comparison with the thin ideal might be the most pronounced. To test this prediction, one hundred and seventy-three young female participants were exposed to images of the thin ideal or of women’s fashion accessories. They were allocated to either a condition of high (memorizing 10 digits) or low cognitive load (memorizing 4 digits). The main dependent measure was implicit: mean recognition latency of negative words, relative to neutral words, as assessed by a lexical decision task. The results showed that thin-ideal exposure did not affect negative word accessibility under low cognitive load but that it increased it under high cognitive load. These findings are consistent with the hypothesis that social comparison with the thin ideal is an automatic process, and contribute to explain why some strategies to prevent negative effects of thin-ideal exposure are inefficient. [less ▲]

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See detailDisentangling the role of users' preferences and impulsivity traits in problematic Facebook use.
Rothen, Stephane; Briefer, Jean-Francois; Deleuze, Jory et al

in PloS one (2018), 13(9), 0201971

The use of social network sites (SNSs) has grown dramatically. Numerous studies have shown that SNS users may suffer from excessive use, associated with addictive-like symptoms. With a focus on the ... [more ▼]

The use of social network sites (SNSs) has grown dramatically. Numerous studies have shown that SNS users may suffer from excessive use, associated with addictive-like symptoms. With a focus on the popular SNS Facebook (FB), our aims in the current study were twofold: First, to explore the heterogeneity of FB usage and determine which kind of FB activity predicts problematic usage; second, to test whether specific impulsivity facets predict problematic use of FB. To this end, a sample of FB users (N = 676) completed an online survey assessing usage preferences (e.g., types of activities performed), symptoms of problematic FB use and impulsivity traits. Results indicated that specific usage preferences (updating one's status, gaming via FB, and using notifications) and impulsive traits (positive and negative urgency, lack of perseverance) are associated to problematic FB use. This study underscores that labels such as FB "addiction" are misleading and that focusing on the actual activities performed on SNSs is crucial when considering dysfunctional usage. Furthermore, this study clarified the role of impulsivity in problematic FB use by building on a theoretically driven model of impulsivity that assumes its multidimensional nature. The current findings have identifiable theoretical and public health implications. [less ▲]

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See detailOn the genetic and environmental sources of social and political participation in adolescence and early adulthood
Kornadt, Anna Elena UL; Hufer, Anke; Kandler, Christian et al

in PLOS ONE (2018), 13(8),

Political participation (POP), social participation (SOP), and political interest (PI) are important indicators of social status and social inequality. Previous studies on related trait differences ... [more ▼]

Political participation (POP), social participation (SOP), and political interest (PI) are important indicators of social status and social inequality. Previous studies on related trait differences yielded genetic and environmental contributions. However, focusing on adult samples, classical twin designs, and convenience samples often restricts parameter estimation and generalizability, and limits the understanding of age differences. We investigated sources of variance in POP, SOP, and PI in late adolescence and early adulthood with an extended twin family design (ETFD). We analyzed data from over 2,000 representative German twin families. Individual environments not shared by family members reflected the major source of variance for all variables, but genetic influences were also pronounced. Genetic effects were mostly higher for young adults, whereas effects of twins' shared environment were significant in adolescence. Our study deepens the understanding of the interplay between genetic and environmental factors in shaping differences in young persons' integration in society. [less ▲]

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See detailCalculating the Malliavin derivative of some stochastic mechanics problems
Hauseux, Paul UL; Hale, Jack UL; Bordas, Stéphane UL

in PLoS ONE (2017), 12(12), 0189994

The Malliavin calculus is an extension of the classical calculus of variations from deterministic functions to stochastic processes. In this paper we aim to show in a practical and didactic way how to ... [more ▼]

The Malliavin calculus is an extension of the classical calculus of variations from deterministic functions to stochastic processes. In this paper we aim to show in a practical and didactic way how to calculate the Malliavin derivative, the derivative of the expectation of a quantity of interest of a model with respect to its underlying stochastic parameters, for four problems found in mechanics. The non-intrusive approach uses the Malliavin Weight Sampling (MWS) method in conjunction with a standard Monte Carlo method. The models are expressed as ODEs or PDEs and discretised using the finite difference or finite element methods. Specifically, we consider stochastic extensions of; a 1D Kelvin-Voigt viscoelastic model discretised with finite differences, a 1D linear elastic bar, a hyperelastic bar undergoing buckling, and incompressible Navier-Stokes flow around a cylinder, all discretised with finite elements. A further contribution of this paper is an extension of the MWS method to the more difficult case of non-Gaussian random variables and the calculation of second-order derivatives. We provide open-source code for the numerical examples in this paper. [less ▲]

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See detailRejection sensitivity as a vulnerability marker for depressive symptom deterioration in men.
De Rubeis, Jannika; Lugo, Ricardo; Witthöft, Michael et al

in PLoS ONE (2017), 12(10), 0185802

Consistent across time and cultures, men and male adolescents older than 14 years of age appear underrepresented in mood disorders, and are far less likely than women to seek psychological help. The much ... [more ▼]

Consistent across time and cultures, men and male adolescents older than 14 years of age appear underrepresented in mood disorders, and are far less likely than women to seek psychological help. The much higher rate of suicide amongst males suggests that depression in men might be underreported. One of the core human motives is to seek acceptance by others and avoid rejection. Rejection Sensitivity (RS) has been conceptualized as the cognitive-affective processing disposition to anxiously expect, readily perceive, and intensely respond to cues of rejection in the behavior of others. RS has been previously linked with the onset and course of depression, but - as yet - has not been investigated longitudinally in a clinical population. We investigated the predictive role of RS to symptom deterioration 6 months after end-of- treatment in 72 male inpatients with depressive spectrum disorder. The BDI was administered at intake, end-of-treatment and 6 month follow-up. RS scores were obtained at intake. Rejection Sensitivity had additional predictive power on BDI scores at 6 months follow-up controlling for BDI scores at end-of-treatment (ΔR2 = .095). The results are discussed in terms of the importance of targeting RS during treatment, and highlight the fact that therapeutic follow-up care is paramount. Future research should investigate possible mediators of the RS- relapse-to-depression association, such as self-blame, rumination, neuroticism, pessimism, emotion dysregulation, and low self-esteem. [less ▲]

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See detailProfile formation of academic self-concept in elementary school students in grades 1 to 4
Schmidt, Isabelle; Brunner, Martin UL; Keller, Lena et al

in PLoS ONE (2017), 12(5), 0177854

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See detailBile microbiota in primary sclerosing cholangitis: Impact on disease progression and development of biliary dysplasia
Pereira, P.; Aho, Velma UL; Arola, J. et al

in PLoS ONE (2017), 12(8), 0182924

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See detailThe Water Load Test As a Measure of Gastric Interoception: Development of a Two-Stage Protocol and Application to a Healthy Female Population
Van Dyck, Zoé UL; Vögele, Claus UL; Blechert, Jens et al

in PLoS ONE (2016), 11(9), 0163574

The sensitivity for one’s own internal body signals (i.e., interoception) has been demonstrated to play an important role in the pathogenesis of eating and weight disorders. Most previous measures ... [more ▼]

The sensitivity for one’s own internal body signals (i.e., interoception) has been demonstrated to play an important role in the pathogenesis of eating and weight disorders. Most previous measures assessing interoceptive processing have not, or only partly, captured perception of hunger and satiety cues, which is a core aspect of interoceptive deficits in eating disorders. In addition, methods used to measure sensitivity to gastric signals are heterogeneous and findings inconsistent. The primary aim of the present study was to establish a standardised test to measure gastric interoception, and to provide normative data using a non-clinical adult sample. The two-step Water Load Test (WLT-II) involves ingestion of non-caloric water until perceived satiation (step 1) and until maximum fullness (step 2). The WLT-II consists of several variables: Besides volumes of water ingested until satiation and maximum fullness expressed in ml, percentage of satiation to maximum fullness is calculated as an individual index of gastric interoception that is not confounded with stomach capacity. Ninety-nine healthy women participated in the study. Measures included the WLT-II, the heartbeat tracking test, a self-report questionnaire assessing subjective sensations, and the Eating Disorder Inventory-2. Twenty-eight participants underwent test-retest of the WLT-II. Results suggest that the WLT-II is a valid and reliable measure of gastric interoception. Importantly, satiation volume and percentage of satiation to maximum fullness were strongly positively related to self-reported bulimic symptoms, indicating that the WLT-II could emerge as a useful clinical tool to measure interoceptive processing in the field of eating disorders. [less ▲]

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See detailAlpha-Synuclein Proteins Promote Pro-Inflammatory Cascades in Microglia: Stronger Effects of the A53T Mutant.
Hoenen, Claire; Gustin, Audrey; Birck, Cindy et al

in PLoS ONE (2016)

Parkinson’s disease (PD) is histologically described by the deposition of α-synuclein, whose accumulation in Lewy bodies causes dopaminergic neuronal death. Although most of PD cases are sporadic, point ... [more ▼]

Parkinson’s disease (PD) is histologically described by the deposition of α-synuclein, whose accumulation in Lewy bodies causes dopaminergic neuronal death. Although most of PD cases are sporadic, point mutations of the gene encoding the α-synuclein protein cause inherited forms of PD. There are currently six known point mutations that result in familial PD. Oxidative stress and neuroinflammation have also been described as early events associated with dopaminergic neuronal degeneration in PD. Though it is known that microglia are activated by wild-type α-synuclein, little is known about its mutated forms and the signaling cascades responsible for this microglial activation. The present study was designed to investigate consequences of wild-type and mutant α-synuclein (A53T, A30P and E46K) exposure on microglial reactivity. Interestingly, we described that α-synuclein-induced microglial reactivity appeared to be peptide-dependent. Indeed, the A53T protein activated more strongly microglia than the wild-type α-synuclein and other mutants. This A53T-induced microglial reactivity mechanism was found to depend on phosphorylation mechanisms mediated by MAPKs and on successive NFkB/AP-1/Nrf2 pathways activation. These results suggest that the microgliosis intensity during PD might depend on the type of α-synuclein protein implicated. Indeed, mutated forms are more potent microglial stimulators than wild-type α-synuclein. Based on these data, anti-inflammatory and antioxidant therapeutic strategies may be valid in order to reduce microgliosis but also to subsequently slow down PD progression, especially in familial cases. [less ▲]

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See detailTesting persistence of cohort effects in the epidemiology of suicide: an age-period-cohort hysteresis model
Chauvel, Louis UL; Leist, Anja UL; Ponomarenko, Valentina UL

in PLoS ONE (2016)

Birth cohort effects in suicide rates are well established, but to date there is no methodological approach or framework to test the temporal stability of these effects. We use the APC-Detrended (APCD ... [more ▼]

Birth cohort effects in suicide rates are well established, but to date there is no methodological approach or framework to test the temporal stability of these effects. We use the APC-Detrended (APCD) model to robustly estimate intensity of cohort effects identifying non-linear trends (or ‘detrended’ fluctuations) in suicide rates. The new APC-Hysteresis (APCH) model tests temporal stability of cohort effects. Analysing suicide rates in 25 WHO countries (periods 1970–74 to 2005–09; ages 20–24 to 70–79) with the APCD method, we find that country-specific birth cohort membership plays an important role in suicide rates. Among 25 countries, we detect 12 nations that show deep contrasts among cohort-specific suicide rates including Italy, Australia and the United States. The APCH method shows that cohort fluctuations are not stable across the life course but decline in Spain, France and Australia, whereas they remain stable in Italy, the United Kingdom and the Netherlands. We discuss the Spanish case with elevated suicide mortality of cohorts born 1965-1975 which declines with age, and the opposite case of the United States, where the identified cohort effects of those born around 1960 increase smoothly, but statistically significant across the life course. [less ▲]

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See detailA Recurrent Germline Mutation in the 5'UTR of the Androgen Receptor Causes Complete Androgen Insensitivity by Activating Aberrant uORF Translation
Hornig, N.C.; De Beaufort, Carine UL; Denzer, F. et al

in PLoS ONE (2016), 11(4),

A subset of patients with monogenic disorders lacks disease causing mutations in the protein coding region of the corresponding gene. Here we describe a recurrent germline mutation found in two unrelated ... [more ▼]

A subset of patients with monogenic disorders lacks disease causing mutations in the protein coding region of the corresponding gene. Here we describe a recurrent germline mutation found in two unrelated patients with complete androgen insensitivity syndrome (CAIS) generating an upstream open reading frame (uORF) in the 5’ untranslated region (5’-UTR) of the androgen receptor (AR) gene. We show in patient derived primary genital skin fibroblasts as well as in cell-based reporter assays that this mutation severely impacts AR function by reducing AR protein levels without affecting AR mRNA levels. Importantly, the newly generated uORF translates into a polypeptide and the expression level of this polypeptide inversely correlates with protein translation from the primary ORF of the AR thereby providing a model for AR-5′UTR mediated translational repression. Our findings not only add a hitherto unrecognized genetic cause to complete androgen insensitivity but also underline the importance of 5′UTR mutations affecting uORFs for the pathogenesis of monogenic disorders in general. [less ▲]

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See detailEvaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes
Lal, Dennis; Reinthaler, Eva; Dejanovic et al

in PLoS ONE (2016)

Objective The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing ... [more ▼]

Objective The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10−4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions. [less ▲]

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See detailGene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages
Antony, Paul UL; Tallam, Aravind UL; Perumal, Thanneer Malai UL et al

in PLoS ONE (2016)

Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein ... [more ▼]

Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFα and IFNγ, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels. [less ▲]

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