Stepwise recombination suppression around the mating-type locus in an ascomycete fungus with self-fertile spores.

Recombination is often suppressed at sex-determining loci in plants and animals, and at self-incompatibility or mating-type loci in plants and fungi. In fungal ascomycetes, recombination suppression around the mating-type locus is associated with pseudo-homothallism, i.e. the production of self-fertile dikaryotic sexual spores carrying the two opposite mating types. This has been well studied in two species complexes from different families of Sordariales: Podospora anserina and Neurospora tetrasperma. However, it is unclear whether this intriguing association holds in other species. We show here that Schizothecium tetrasporum, a fungus from a third family in the order Sordariales, also produces mostly self-fertile dikaryotic spores carrying the two opposite mating types. This was due to a high frequency of second meiotic division segregation at the mating-type locus, indicating the occurrence of a single and systematic crossing-over event between the mating-type locus and the centromere, as in P. anserina. The mating-type locus has the typical Sordariales organization, plus a MAT1-1-1 pseudogene in the MAT1-2 haplotype. High-quality genome assemblies of opposite mating types and segregation analyses revealed a suppression of recombination in a region of 1.47 Mb around the mating-type locus. We detected three evolutionary strata, indicating a stepwise extension of recombination suppression. The three strata displayed no rearrangement or transposable element accumulation but gene losses and gene disruptions were present, and precisely at the strata margins. Our findings indicate a convergent evolution of self-fertile dikaryotic sexual spores across multiple ascomycete fungi. The particular pattern of meiotic segregation at the mating-type locus was associated with recombination suppression around this locus, that had extended stepwise. This association between pseudo-homothallism and recombination suppression across lineages and the presence of gene disruption at the strata limits are consistent with a recently proposed mechanism of sheltering deleterious alleles to explain stepwise recombination suppression.

Genome-scale phylogeny and comparative genomics of the fungal order Sordariales.

The order Sordariales is taxonomically diverse, and harbours many species with different lifestyles and large economic importance. Despite its importance, a robust genome-scale phylogeny, and associated comparative genomic analysis of the order is lacking. In this study, we examined whole-genome data from 99 Sordariales, including 52 newly sequenced genomes, and seven outgroup taxa. We inferred a comprehensive phylogeny that resolved several contentious relationships amongst families in the order, and cleared-up intrafamily relationships within the Podosporaceae. Extensive comparative genomics showed that genomes from the three largest families in the dataset (Chaetomiaceae, Podosporaceae and Sordariaceae) differ greatly in GC content, genome size, gene number, repeat percentage, evolutionary rate, and genome content affected by repeat-induced point mutations (RIP). All genomic traits showed phylogenetic signal, and ancestral state reconstruction revealed that the variation of the properties stems primarily from within-family evolution. Together, the results provide a thorough framework for understanding genome evolution in this important group of fungi.

Caregivers in anorexia nervosa: is grief underlying parental burden?

ABSTARCT: PURPOSE: Anorexia Nervosa (AN) is a severe chronic disorder and parents' experience of caregiving is usually marked by emotional distress and burden. Severe chronic psychiatric disorders are known to be linked with the concept of grief. Grief has not been investigated in AN. The aim of this study was to explore parents' and adolescents' characteristics that may be related to parental burden and grief in AN, and the link between these two dimensions. METHODS: Eighty mothers, 55 fathers and their adolescents (N = 84) hospitalized for AN participated in this study. Evaluations of clinical characteristics of the adolescent's illness were completed, as well as self-evaluations of adolescent and parental emotional distress (anxiety, depression, alexithymia). Levels of parental burden were evaluated with the Experience of Caregiving Inventory and levels of parental grief with the Mental Illness Version of the Texas Revised Inventory of Grief. RESULTS: Main findings indicated that the burden was higher in parents of adolescents with a more severe AN; fathers' burden was also significantly and positively related to their own level of anxiety. Parental grief was higher when adolescents' clinical state was more severe. Paternal grief was related to higher anxiety and depression, while maternal grief was correlated to higher alexithymia and depression. Paternal burden was explained by the father's anxiety and grief, maternal burden by the mother's grief and her child's clinical state. CONCLUSION: Parents of adolescents suffering from AN showed high levels of burden, emotional distress and grief. These inter-related experiences should be specific targets for intervention aimed at supporting parents. Our results support the extensive literature on the need to assist fathers and mothers in their caregiving role. This in turn may improve both their mental health and their abilities as caregivers of their suffering child. LEVEL OF EVIDENCE: Level III: Evidence obtained from cohort or case-control analytic studies.

Patients' high acceptability of a future therapeutic HIV vaccine in France: a French paradox?

BACKGROUND: France is the European country with the lowest level of confidence in vaccines. Measurement of patients' acceptability towards a future therapeutic HIV vaccine is critically important. Thus, the aim of this study was to evaluate patients' acceptability of a future therapeutic HIV vaccine in a representative cohort of French patients living with HIV-AIDS (PLWHs). METHODS: This multicentre study used quantitative and qualitative methods to assess PLWHs' opinions and their potential acceptance of a future therapeutic HIV vaccine. Cross-sectional study on 220 HIV-1 infected outpatients, aged 18-75 years. RESULTS: The participants' characteristics were similar to those of the overall French PLWH population. Responses from the questionnaires showed high indices of acceptance: the mean score for acceptability on the Visual Analog Scale VAS was 8.4 of 10, and 92% of patients agreed to be vaccinated if a therapeutic vaccine became available. Acceptability depended on the expected characteristics of the vaccine, notably the duration of its effectiveness: 44% of participants expected it to be effective for life. This acceptance was not associated with socio-demographic, clinical (mode of contamination, duration of disease), quality of life, or illness-perception parameters. Acceptability was also strongly correlated with confidence in the treating physician. CONCLUSION: The PLWHs within our cohort had high indices of acceptance to a future therapeutic HIV vaccine. TRIAL REGISTRATION: This study was retroactively registered on ClinicalTrials.gov with ID: NCT02077101 in February 21, 2014.

High-intensity exercise is associated with a better nutritional status in anorexia nervosa.

OBJECTIVE: Our aim is to investigate the links between duration and intensity of exercise and the nutritional status in terms of body composition in acute anorexia nervosa (AN) patients. METHOD: One hundred ninety-one hospitalized women suffering from AN were included. Exercise duration and intensity were assessed using a semistructured questionnaire. Body composition was measured using bioelectrical impedance. Linear multiple regression analyses were carried out using body mass index, fat-free mass index, and fat mass index as dependent variables and including systematically exercise duration, exercise intensity, and other confounding variables described in the literature that were significantly associated with each dependent variable in univariate analysis. RESULTS: A lower BMI was linked to lower exercise intensity, AN restrictive type, and presence of amenorrhea. A lower FFMI was linked to lower exercise intensity, older age, AN restrictive type, and premenarchal AN. Duration of exercise was not linked to the nutritional status. CONCLUSIONS: Exercising at higher intensity in AN is associated with a better nutritional status, thus, a better resistance to starvation. The impact of therapeutic physical activity sessions, adapted in terms of exercise intensity and patient's clinical status, should be evaluated during nutrition rehabilitation.

Barriers to publishing in biomedical journals perceived by a sample of French researchers: results of the DIAzePAM study.

BACKGROUND: As publishing is essential but competitive for researchers, difficulties in writing and submitting medical articles to biomedical journals are disabling. The DIAzePAM (Difficultés des Auteurs à la Publication d'Articles Médicaux) survey aimed to assess the difficulties experienced by researchers in the AP-HP (Assistance Publique - Hôpitaux de Paris, i.e., Paris Hospitals Board, France), the largest public health institution in Europe, when preparing articles for biomedical journals. The survey also aimed to assess researchers' satisfaction and perceived needs. METHODS: A 39-item electronic questionnaire based on qualitative interviews was addressed by e-mail to all researchers registered in the AP-HP SIGAPS (Système d'Interrogation, de Gestion et d'Analyse des Publications Scientifiques) bibliometric database. RESULTS: Between 28 May and 15 June 2015, 7766 researchers should have received and read the e-mail, and 1191 anonymously completed the questionnaire (<45 years of age: 63%; women: 55%; physician: 81%; with PhD or Habilitation à Diriger des recherches--accreditation to direct research--: 45%). 94% of respondents had published at least one article in the previous 2 years. 76% of respondents felt they were not publishing enough, mainly because of lack of time to write (79%) or submit (27%), limited skills in English (40%) or in writing (32%), and difficulty in starting writing (35%). 87% of respondents would accept technical support, especially in English reediting (79%), critical reediting (63%), formatting (52%), and/or writing (41%), to save time (92%) and increase high-impact-factor journal submission and acceptance (75%). 79% of respondents would appreciate funding support for their future publications, for English reediting (56%), medical writing (21%), or publication (38%) fees. They considered that this funding support could be covered by AP-HP (73%) and/or by the added financial value obtained by their department from previous publications (56%). CONCLUSIONS: The DIAzePAM survey highlights difficulties experienced by researchers preparing articles for biomedical journals, and details room for improvement.

The International development of PROQOL-HCV: An instrument to assess the health-related quality of life of patients treated for Hepatitis C virus.

BACKGROUND: Hepatitis C virus (HCV) compromises Health-related Quality of Life (HRQL) with detriments to Physical, Mental and Social health domains. Treatment with interferon and ribavirin is associated with side effects which further impair HRQL. New treatments appear potent, effective and tolerable. However, Patient Reported Outcomes instruments that capture the impact on HRQL for people with hepatitis C are largely non-specific and will be needed in the new treatment era. Therefore, we developed a conceptually valid multidimensional model of HCV-specific quality of life and pilot survey instrument, the Patient Reported Outcome Quality of Life survey for HCV (PROQOL-HCV). METHODS: HCV patients from France (n = 30), Brazil (n = 20) and Australia (n = 20) were interviewed to investigate HCV-HRQL issues raised in the scientific literature and by treatment specialists. Interviews were recorded, transcribed and translated into English and French. RESULTS: Fifteen content dimensions were derived from the qualitative analysis, refined and fitted to four domains: (1) Physical Health included: fatigue, pain, sleep, sexual impairment and physical activity; (2) Mental Health: psychological distress, psychosocial impact, and cognition; (3) Social Health: support, stigma, social activity, substance use; (4) TREATMENT: management, side effects, and fear of treatment failure. The impact of some dimensions extended beyond their primary domain including: physical activity, cognition, sleep, sexual impairment, and the three treatment dimensions. A bank of 300 items was constructed to reflect patient reports and, following expert review, reduced to a 72-item pilot questionnaire. CONCLUSION: We present a conceptually valid multidimensional model of HCV-specific quality of life and the pilot survey instrument, PROQOL-HCV. The model is widely inclusive of the experience of hepatitis C and the first to include the treatment dimension.

Genetic and Environmental Influences on the Visual Word Form and Fusiform Face Areas.

Two areas of the occipitotemporal cortex show a remarkable hemispheric lateralization: written words activate the visual word form area (VWFA) in the left fusiform gyrus and faces activate a symmetrical site in the right hemisphere, the fusiform face area (FFA). While the lateralization of the VWFA fits with the leftward asymmetry of the speech processing network, origin of the rightward asymmetry for faces is still unclear. Using fMRI data from 64 subjects (including 16 monozygotic (MZ) and 13 dizygotic (DZ) twin pairs), we investigated how activations evoked by written words, faces, and spoken language are co-lateralized in the temporal lobe, and whether this organization reflects genetic factors or individual reading expertise. We found that the lateralization of the left superior temporal activation for spoken language correlates with the lateralization of occipitotemporal activations for both written words and faces. Behavioral reading scores also modulate the responses to words and faces. Estimation of genetic and environmental contributions shows that activations of the VWFA, the occipital face area, and the temporal speech areas are partially under genetic control whereas activation of the FFA is primarily influenced by individual experience. Our results stress the importance of both genetic factors and acquired expertise in the occipitotemporal organization.

Psychometric assessment of health-related quality of life and symptom experience in HIV patients treated with antiretroviral therapy.

PURPOSE: Symptoms which are found to cluster consistently can have synergistic effects on patient outcomes and therefore may serve to predict morbidity or disentangle disease progression from comorbid conditions. Self-report HIV-specific symptom and HRQL measures were jointly analyzed in HIV-positive patients under different antiretroviral treatment regimens. METHODS: The responses of N = 365 patients from four countries to the 9-item Physical Health and Symptom dimension of the PROOQL-HIV questionnaire and an HIV Symptom checklist were analyzed. Item response modeling and multidimensional scaling were used to derive HRQL scores free of any differential item functioning related to gender and target language and to summarize symptom co-expression in patients under protease inhibitor treatment(PI, N = 164, 45%) versus other medication (Non-PI). RESULTS: Women reported poorer HRQL (p = 0:037), and HRQL did not differ between the target languages of French, English, and Thai. Fatigue, muscular pain, or difficulties falling asleep was the most frequently reported symptoms [35%). PI versus Non-PI patients exhibited different pattern of symptoms with lipodystrophy-related and gastrointestinal symptoms forming well-separated clusters in the PI group. A higher number of symptoms were associated with lower HRQL (p < 0:001), and patients taking PIs reported lower HRQL (p = 0:003). Patients in both groups who reported fatigue, sexual dysfunction, or several lipodystrophy-related symptoms had poorer quality of life.

Alexithymia, a compounding factor for eating and social avoidance symptoms in anorexia nervosa.

Socio-affective difficulties, in particular difficulties in representing, communicating and feeling emotions, may play a critical role in anorexia nervosa (AN). The aim of this longitudinal study was to explore the links between alexithymia and two types of difficulties in AN: eating symptoms and social avoidance. Sixty adolescent girls with AN were recruited following hospitalisation in a specialised department. They completed self-administered questionnaires of alexithymia (TAS-20), of central symptoms of the eating disorders (EDI), and of anxious and depressive affects (SCL-90). Anxiety and social avoidance were assessed in the course of a standardised interview (LSAS). These measures were performed at inclusion, and at 6-, 12- and 18-months' follow-up. The relationship between TAS-20 and EDI or LSAS total scale scores across the four time points was assessed using mixed-effects models, including anxiety, depression, BMI, anorexia subtype, and age as co-factors. Partial least square regression was used to refine this multivariate analysis at subscale level, at inclusion and 18 months. Robust associations between TAS-20 and EDI scores were found, independently from anxious and depressive scores, nutritional state and AN subtype. These effects appeared more particularly linked to the implication of the dimensions difficulties identifying and describing feelings, interpersonal mistrust, feelings of inadequacy and interoceptive awareness deficit. There was also a durable association between alexithymia and social anxiety and avoidance, after adjusting for the confounding effects of depression, and anxiety, and the state of starvation. Difficulties in describing feelings appeared particularly involved here. Thus alexithymia does appear as a factor in the persistence of disorders in AN, and difficulties identifying and describing feelings could compound the social difficulties and major the relational isolation of these patients.

The influence of eating disorders on mothers' sensitivity and adaptation during feeding: a longitudinal observational study.

BACKGROUND: Parents with past and current eating disorders (ED) have been shown to report troubles nourishing their infants. This could increase the risk of infant feeding problems linked to maternal anxiety and depression. It is not clear how mothers' eating difficulties before pregnancy and at the time of birth can affect infant's feeding. We aimed to specify the impact of eating disorders on mothers' adaptation and sensitivity to their offspring during feeding, by comparing a population of mothers with eating disorders and controls. METHODS: Twenty-eight women agreed to participate in interviews and filmed mother-baby interactions. Pregnant women consulting at an obstetric unit for care follow-up were screened and tested for symptoms of eating disorders with the EDE-Q Questionnaire (Eating Disorders Examination Questionnaire) and the EDE Interview (Eating Disorders Examination Interview). Infant functional troubles and mothers' sensitivity were investigated through the Symptom Check List. Reciprocal adaptation during feeding with their new-borns was filmed and analysed with the Chatoor Infant Feeding Scale. Before pregnancy, two women suffered from anorexia, three suffered from bulimia, three had binge eating symptoms and two were diagnosed with EDNOS (Eating Disorders Not Otherwise Specified). RESULTS: Mothers suffering from ED tended to show more difficult interactive patterns in terms of dyadic reciprocity when feeding their babies compared with mothers with no symptoms of eating disorders. In the interviews, other than the behavioural data gathered, ED mothers expressed feeling more dissatisfaction and uneasiness during feeding. CONCLUSIONS: Pregnancy seems to be an useful period for interviewing women on eating disorders, allowing for the design and implementation of prevention programmes based on mothers' narratives and infant/mother observations and treatment.

Electronic versus paper-based assessment of health-related quality of life specific to HIV disease: reliability study of the PROQOL-HIV questionnaire.

BACKGROUND: Electronic patient-reported outcomes (PRO) provide quick and usually reliable assessments of patients' health-related quality of life (HRQL). OBJECTIVE: An electronic version of the Patient-Reported Outcomes Quality of Life-human immunodeficiency virus (PROQOL-HIV) questionnaire was developed, and its face validity and reliability were assessed using standard psychometric methods. METHODS: A sample of 80 French outpatients (66% male, 52/79; mean age 46.7 years, SD 10.9) were recruited. Paper-based and electronic questionnaires were completed in a randomized crossover design (2-7 day interval). Biomedical data were collected. Questionnaire version and order effects were tested on full-scale scores in a 2-way ANOVA with patients as random effects. Test-retest reliability was evaluated using Pearson and intraclass correlation coefficients (ICC, with 95% confidence interval) for each dimension. Usability testing was carried out from patients' survey reports, specifically, general satisfaction, ease of completion, quality and clarity of user interface, and motivation to participate in follow-up PROQOL-HIV electronic assessments. RESULTS: Questionnaire version and administration order effects (N=59 complete cases) were not significant at the 5% level, and no interaction was found between these 2 factors (P=.94). Reliability indexes were acceptable, with Pearson correlations greater than .7 and ICCs ranging from .708 to .939; scores were not statistically different between the two versions. A total of 63 (79%) complete patients' survey reports were available, and 55% of patients (30/55) reported being satisfied and interested in electronic assessment of their HRQL in clinical follow-up. Individual ratings of PROQOL-HIV user interface (85%-100% of positive responses) confirmed user interface clarity and usability. CONCLUSIONS: The electronic PROQOL-HIV introduces minor modifications to the original paper-based version, following International Society for Pharmacoeconomics and Outcomes Research (ISPOR) ePRO Task Force guidelines, and shows good reliability and face validity. Patients can complete the computerized PROQOL-HIV questionnaire and the scores from the paper or electronic versions share comparable accuracy and interpretation.

Characterization of spatio-temporal dynamics of the constrained network of the filamentous fungus Podospora anserina using a geomatics-based approach.

In their natural environment, fungi are subjected to a wide variety of environmental stresses which they must cope with by constantly adapting the architecture of their growing network. In this work, our objective was to finely characterize the thallus development of the filamentous fungus Podospora anserina subjected to different constraints that are simple to implement in vitro and that can be considered as relevant environmental stresses, such as a nutrient-poor environment or non-optimal temperatures. At the Petri dish scale, the observations showed that the fungal thallus is differentially affected (thallus diameter, mycelium aspect) according to the stresses but these observations remain qualitative. At the hyphal scale, we showed that the extraction of the usual quantities (i.e. apex, node, length) does not allow to distinguish the different thallus under stress, these quantities being globally affected by the application of a stress in comparison with a thallus having grown under optimal conditions. Thanks to an original geomatics-based approach based on the use of automatized Geographic Information System (GIS) tools, we were able to produce maps and metrics characterizing the growth dynamics of the networks and then to highlight some very different dynamics of network densification according to the applied stresses. The fungal thallus is then considered as a map and we are no longer interested in the quantity of material (hyphae) produced but in the empty spaces between the hyphae, the intra-thallus surfaces. This study contributes to a better understanding of how filamentous fungi adapt the growth and densification of their network to potentially adverse environmental changes.

HIV-related stigma and physical symptoms have a persistent influence on health-related quality of life in Australians with HIV infection.

BACKGROUND: The health-related quality of life (HRQL) of people living with HIV infection is an important consideration in HIV management. The PROQOL-HIV psychometric instrument was recently developed internationally as a contemporary, discriminating HIV-HRQL measure incorporating influential emotional dimensions such as stigma. Here we present the first within-country results of PROQOL-HIV using qualitative and quantitative data collected from a West Australian cohort who participated in the development and validation of PROQOL-HIV, and provide a comprehensive picture of HRQL in our setting. METHODS: We carried out a secondary analysis of data from Australian patients who participated in the international study: 15 in-depth interviews were conducted and 102 HRQL surveys using the PROQOL-HIV instrument and a symptom questionnaire were administered. We employed qualitative methods to extract description from the interview data and linear regression for exploration of the composite and sub-scale scores derived from the survey. RESULTS: Interviews revealed the long-standing difficulties of living with HIV, particularly in the domains of intimate relationships, perceived stigma, and chronic ill health. The novel PROQOL-HIV instrument discriminated impact of treatment via symptomatology, pill burden and treatment duration. Patients demonstrated lower HRQL if they were: newly diagnosed (p=0.001); naive to anti-retroviral treatment (p=0.009); reporting depression, unemployment or a high frequency of adverse symptoms, (all p<0.001). Total HRQL was notably reduced by perceived stigma with a third of surveyed patients reporting persistent fears of both disclosing their HIV status and infecting others. CONCLUSIONS: The analysis showed that psychological distress was a major influence on HRQL in our cohort. This was compounded in people with poor physical health which in turn was associated with unemployment and depression. People with HIV infection are living longer and residual side effects of the earlier regimens complicate current clinical management and affect their quality of life. However, even for the newly diagnosed exposed to less toxic regimens, HIV-related stigma exerts negative social and psychological effects. It is evident that context-specific interventions are required to address persistent distress related to stigma, reframe personal and public perceptions of HIV infection and ameliorate its disabling social and psychological effects.

Levels of autistic traits in anorexia nervosa: a comparative psychometric study.

BACKGROUND: A number of characteristics associated with Autism Spectrum Disorders (ASD) are over-represented among patients with Anorexia Nervosa (AN) as well as among relatives of these patients. Yet the co-occurrence of autistic traits in AN has not been fully explored and no previous study has directly compared self-reported evaluations of cognitive and socio-affective skills in AN and ASD. METHODS: We aimed to determine the degree of overlap between AN and ASD from scores on questionnaires classically used to measure ASD impairments. Fifteen AN participants, 15 ASD participants and two groups of matched controls completed a battery of self-reports measuring: autistic traits (Autism-Spectrum Quotient), empathy (Empathy Quotient-short and Interpersonal Reactivity Index), systemizing (Systemizing Quotient-short) and alexithymia (Bermond-Vorst Alexithymia Questionnaire-B). Univariate comparisons of mean totalled scores were performed on each measure (patients vs. controls, and AN vs. ASD), and a Principal Component Analysis was used to study subject proximities in a reduced-factor space constructed from AQ, BVAQ-B and IRI subscales. RESULTS: These analyses revealed similarities in a few cognitive domains (Attention Switching, Perspective Taking and Fantasy, lack of emotional introspection) and in some nonspecific affective dimensions (depression and feelings of distress), but also marked dissimilarities in social skills (the ability to communicate emotions to others, empathizing). CONCLUSION: The AN and ASD participants reported similar needs for sameness, and similar difficulties understanding their emotions and taking the perspective of another, but contrasting abilities to feel concerned in interpersonal situations. Our mixed findings encourage further exploration of transdiagnostic similarities and associations between these disorders.

GUN Mutants: New Weapons To Unravel Ascospore Germination Regulation in the Model Fungus Podospora anserina.

In Podospora anserina as in many other Ascomycetes, ascospore germination is a regulated process that requires the breaking of dormancy. Despite its importance in survival and dispersal, ascospore germination in filamentous fungi has been poorly investigated, and little is known about its regulation and genetic control. We have designed a positive genetic screen that led to the isolation of mutants showing uncontrolled germination, the GUN (Germination UNcontrolled) mutants. Here, we report on the characterization of the gun1SG (Spontaneous Germination) mutant. We show that gun1SG is mutated in Pa_6_1340, the ortholog of Magnaporthe oryzae Pth2, which encodes a carnitine-acetyltransferase (CAT) involved in the shuttling of acetyl coenzyme A between peroxisomes and mitochondria and which is required for appressorium development. Bioinformatic analysis revealed that the mutated residue (I441) is highly conserved among Fungi and that the mutation has a deleterious impact on the protein function. We show that GUN1 is essential for ascospore germination and that the protein is localized both in mitochondria and in peroxisomes. Finally, epistasis studies allowed us to place GUN1 together with the PaMpk2 MAPK pathway upstream of the PaNox2/PaPls1 complex in the regulation of ascospore germination. In addition, we show that GUN1 plays a role in appressorium functioning. The pivotal role of GUN1, the ortholog of Pth2, in ascospore germination and in appressorium functioning reinforces the idea of a common genetic regulation governing both appressorium development and melanized ascospore germination. Furthermore, we characterize the second CAT encoded in P. anserina genome, Pa_3_7660/GUP1, and we show that the function of both CATs is conserved in P. anserina. IMPORTANCE The regulation of ascospore germination in filamentous fungi has been poorly investigated so far. To unravel new genes involved in this regulation pathway, we conducted a genetic screen in Podospora anserina, and we isolated 57 mutants affected in ascospore germination. Here, we describe the Germination UNcontrolled One (gun1SG) mutant, and we characterize the gene affected. GUN1 is a peroxisomal/mitochondrial carnitine-acetyltransferase required for acetyl coenzyme A shuttling between both organelles, and we show that GUN1 is a pleiotropic gene also involved in appressorium functioning similarly to its ortholog, the pathogenesis factor Pth2, in the plant pathogen Magnaporthe oryzae. Given the similarities in the regulation of appressorium development and ascospore germination, we speculate that discovering new genes controlling ascospore germination in P. anserina may lead to the discovery of new pathogenesis factors in pathogenic fungi. The characterization of GUN1, the ortholog of M. oryzae Pth2, represents a proof of concept.

Prediction and experimental evidence of different growth phases of the Podospora anserina hyphal network.

Under ideal conditions, the growth of the mycelial network of a filamentous fungus is monotonous, showing an ever increasing complexity with time. The components of the network growth are very simple and based on two mechanisms: the elongation of each hypha, and their multiplication by successive branching. These two mechanisms are sufficient to produce a complex network, and could be localized only at the tips of hyphae. However, branching can be of two types, apical or lateral, depending on its location on the hyphae, therefore imposing the redistribution of the necessary material in the whole mycelium. From an evolutionary point of view, maintaining different branching processes, with additional energy needs for structure and metabolism, is intriguing. We propose in this work to discuss the advantages of each branching type using a new observable for the network growth, allowing us to compare growth configurations. For this purpose, we build on experimental observations of the Podospora anserina mycelium growth, enabling us to feed and constrain a lattice-free modeling of this network based on a binary tree. First, we report the set of statistics related to the branches of P. anserina that we have implemented into the model. Then, we build the density observable, allowing us to discuss the succession of growth phases. We predict that density over time is not monotonic, but shows a decay growth phase, clearly separated from an other one by a stationary phase. The time of appearance of this stable region appears to be driven solely by the growth rate. Finally, we show that density is an appropriate observable to differentiate growth stress.

Significant correlation between a set of genetic polymorphisms and a functional brain network revealed by feature selection and sparse Partial Least Squares.

Brain imaging is increasingly recognised as an intermediate phenotype to understand the complex path between genetics and behavioural or clinical phenotypes. In this context, a first goal is to propose methods to identify the part of genetic variability that explains some neuroimaging variability. Classical univariate approaches often ignore the potential joint effects that may exist between genes or the potential covariations between brain regions. In this paper, we propose instead to investigate an exploratory multivariate method in order to identify a set of Single Nucleotide Polymorphisms (SNPs) covarying with a set of neuroimaging phenotypes derived from functional Magnetic Resonance Imaging (fMRI). Recently, Partial Least Squares (PLS) regression or Canonical Correlation Analysis (CCA) have been proposed to analyse DNA and transcriptomics. Here, we propose to transpose this idea to the DNA vs. imaging context. However, in very high-dimensional settings like in imaging genetics studies, such multivariate methods may encounter overfitting issues. Thus we investigate the use of different strategies of regularisation and dimension reduction techniques combined with PLS or CCA to face the very high dimensionality of imaging genetics studies. We propose a comparison study of the different strategies on a simulated dataset first and then on a real dataset composed of 94 subjects, around 600,000 SNPs and 34 functional MRI lateralisation indexes computed from reading and speech comprehension contrast maps. We estimate the generalisability of the multivariate association with a cross-validation scheme and demonstrate the significance of this link, using a permutation procedure. Univariate selection appears to be necessary to reduce the dimensionality. However, the significant association uncovered by this two-step approach combining univariate filtering and L1-regularised PLS suggests that discovering meaningful genetic associations calls for a multivariate approach.

Refining developmental coordination disorder subtyping with multivariate statistical methods.

BACKGROUND: With a large number of potentially relevant clinical indicators penalization and ensemble learning methods are thought to provide better predictive performance than usual linear predictors. However, little is known about how they perform in clinical studies where few cases are available. We used Random Forests and Partial Least Squares Discriminant Analysis to select the most salient impairments in Developmental Coordination Disorder (DCD) and assess patients similarity. METHODS: We considered a wide-range testing battery for various neuropsychological and visuo-motor impairments which aimed at characterizing subtypes of DCD in a sample of 63 children. Classifiers were optimized on a training sample, and they were used subsequently to rank the 49 items according to a permuted measure of variable importance. In addition, subtyping consistency was assessed with cluster analysis on the training sample. Clustering fitness and predictive accuracy were evaluated on the validation sample. RESULTS: Both classifiers yielded a relevant subset of items impairments that altogether accounted for a sharp discrimination between three DCD subtypes: ideomotor, visual-spatial and constructional, and mixt dyspraxia. The main impairments that were found to characterize the three subtypes were: digital perception, imitations of gestures, digital praxia, lego blocks, visual spatial structuration, visual motor integration, coordination between upper and lower limbs. Classification accuracy was above 90% for all classifiers, and clustering fitness was found to be satisfactory. CONCLUSIONS: Random Forests and Partial Least Squares Discriminant Analysis are useful tools to extract salient features from a large pool of correlated binary predictors, but also provide a way to assess individuals proximities in a reduced factor space. Less than 15 neuro-visual, neuro-psychomotor and neuro-psychological tests might be required to provide a sensitive and specific diagnostic of DCD on this particular sample, and isolated markers might be used to refine our understanding of DCD in future studies.