Implementing citation management and report generation value-added services over OAI-PMH compliant repositories

The National Documentation Center (EKT) has developed HELIOS (http://helios-eie.ekt.gr) - the institutional repository of the National Hellenic Research Foundation (NHRF) aiming at collecting the scientific work of its associate researchers. DSpace has been used as the repository platform in the implementation of HELIOS. According to the repository literature (A DRIVER’s Guide to European Repositories, Amsterdam University Press, 2008), offering value-added services to researchers can be an important factor for repository take-up, able to significantly increase deposits through self-archiving. Therefore, in order to encourage the usage of HELIOS among the NHRF researchers, an application providing value-added services over the repository has been developed. In brief, this application harvests the digital repository's data and presents them outside the repository's framework, enabling citation management and configurable custom reporting, for example producing publication lists per researcher and institute, exactly in the format applied in the institute annual report. The application is in operation on top of the HELIOS DSpace-based repository; however it has been designed and implemented to depend only on information retrieved via OAI-PMH, so that it can work with any OAI-PMH compliant repository platform (DSpace, Eprints, Fedora, etc.

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Implementing citation management and report generation value-added services over OAI-PMH compliant repositories

he National Documentation Center (EKT) has developed HELIOS (http://helios-eie.ekt.gr) - the institutional repository of the National Hellenic Research Foundation (NHRF) aiming at collecting the scientific work of its associate researchers. DSpace has been used as the repository platform in the implementation of HELIOS. According to the repository literature (A DRIVER’s Guide to European Repositories, Amsterdam University Press, 2008), offering value-added services to researchers can be an important factor for repository take-up, able to significantly increase deposits through self-archiving. Therefore, in order to encourage the usage of HELIOS among the NHRF researchers, an application providing value-added services over the repository has been developed. In brief, this application harvests the digital repository's data and presents them outside the repository's framework, enabling citation management and configurable custom reporting, for example producing publication lists per researcher and institute, exactly in the format applied in the institute annual report. The application is in operation on top of the HELIOS DSpace-based repository; however it has been designed and implemented to depend only on information retrieved via OAI-PMH, so that it can work with any OAI-PMH compliant repository platform (DSpace, Eprints, Fedora, etc.

The Role of Astrocytes In Parkinson’s Disease: A Cellular And Molecular Study

Η νόσος του Πάρκινσον (ΝΠ) είναι η δεύτερη πιο συχνή νευροεκφυλιστική διαταραχή μετά τη νόσο του Αλτσχάιμερ (ΝΑ) και προσβάλλει περίπου το 1% των ατόμων άνω των 60 ετών. Οι κλινικές εκδηλώσεις της νόσου περιλαμβάνουν τόσο κινητικά συμπτώματα, όπως τρόμο, ακαμψία, αστάθεια στάσης και ακινησία/βραδυκινησία, όσο και μη κινητικά συμπτώματα, όπως άνοια, υποσμία και διαταραχές ύπνου. Η ΝΠ είναι μέχρι σήμερα ανίατη, πιθανότατα λόγω της ελλιπούς κατανόησης των μηχανισμών της νόσου σε σχέση με την μη πρόσβαση σε ανθρώπινο εγκεφαλικό ιστό και την ανεπαρκή συνάφεια των ζωικών μοντέλων. Τα αστροκύτταρα αποτελούν έναν ειδικό κυτταρικό πληθυσμό του εγκεφάλου που έχει προσελκύσει πρόσφατα την προσοχή των ερευνητών για την κρίσιμη συμμετοχή τους στη φυσιολογία και την παθολογία. Για να εξετάσουμε τον ρόλο των αστροκυττάρων ιδιαίτερα στην ΝΠ και να εντοπίσουμε πιθανούς νέους στόχους για τον σχεδιασμό θεραπείας, στην παρούσα μελέτη χρησιμοποιήσαμε μια πρόσφατα αναπτυχθείσα μέθοδο για τη δημιουργία αστροκυττάρων ειδικά για τον ασθενή με τη χρήση βιοψιών δέρματος από ασθενείς με ΝΠ και τα συγκρίναμε με αστροκύτταρα που δημιουργήθηκαν από υγιή δότη. Τα αστροκύτταρα με ΝΠ εμφάνισαν διακριτά παθολογικά χαρακτηριστικά που εμπλέκονται στη λειτουργία τους, υποδηλώνοντας κυτταρικά ελλείμματα που σχετίζονται με την παθολογία της ΝΠ, όπως δυσλειτουργία του συστήματος ελέγχου της ποιότητας των πρωτεϊνών. Προσδοκούμε ότι τα δεδομένα μας θα παράσχουν νέες πληροφορίες σχετικά με τη συμβολή της δυσλειτουργίας των αστροκυττάρων στην παθογένεια της νόσου Πάρκινσον και η πειραματική μας πλατφόρμα θα μπορούσε τελικά να χρησιμεύσει ως μια νέα πλατφόρμα δοκιμής φαρμάκων.Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease (AD), affecting approximately 1% of people above 60. The clinical manifestations of PD include both motor symptoms such as tremor, rigidity, postural instability, and akinesia/bradykinesia and non-motor symptoms, such as dementia, hyposmia, and sleep disorders. PD is to date incurable, likely due to incomplete understanding of the disease mechanisms in relation with inaccessibility of the human brain tissue and inadequate relevance of animal models. Astrocytes comprise a specific cell population of the brain that has recently attracted researchers’ attention for their critical participation in physiology and pathology. To examine the role of astrocytes particularly in PD and identify putative novel targets for treatment design, in this study we used a recently developed method to generate patient-specific astrocytes by using skin biopsies from PD patients and compared them with astrocytes generated from a healthy donor. PD astrocytes displayed distinct pathological characteristics implicated in their function suggesting cellular deficits related with PD pathology, such as protein quality control system dysfunction. We anticipate that our data will provide novel insight into the contribution of astrocytes’ malfunction in PD pathogenesis and our experimental setup could ultimately serve as a new drug-testing platform

On type 1 diabetes mellitus pathogenesis

Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of β cells of the endocrine pancreas. Pathogenesis of type 1 diabetes mellitus is different from that of type 2 diabetes mellitus, where both insulin resistance and reduced secretion of insulin by the β cells play a synergistic role. We will present genetic, environmental and immunologic factors that destroy β cells of the endocrine pancreas and lead to insulin deficiency. The process of autoimmune destruction takes place in genetically susceptible individuals under the triggering effect of one or more environmental factors and usually progresses over a period of many months to years, during which period patients are asymptomatic and euglycemic, but positive for relevant autoantibodies. Symptomatic hyperglycemia and frank diabetes occurs after a long latency period, which reflects the large percentage of β cells that need to be destroyed before overt diabetes become evident

MENSTRUAL DISORDERS AND ANDROGEN-RELATED TRAITS IN YOUNG WOMEN WITH TYPE 1 DIABETES MELLITUS: A CLINICAL STUDY

Objective: To investigate possible causes of menstrual disorders and androgen-related traits in young women with type 1 diabetes mellitus (T1DM). Methods: Fifty-three women with T1DM (duration 8.0 +/- 5.6 years), 41 women with (polycystic ovary syndrome) PCOS, and 51 controls matched for age (19.4 +/- 4.3 years vs. 21.2 +/- 2.7 years vs. 20.8 +/- 3.1 years; P>.05) and body mass index (BMI) (22.2 +/- 2.7 kg/m(2) vs. 21.9 +/- 2.0 kg/m(2) vs. 21.4 +/- 1.9 kg/m(2); P>.05) were prospectively recruited. Results: Two women (3.8%) in the T1DM group had not experienced menarche (at 15.5 and 16.6 years); of the rest, 2.3.5% had oligomenorrhea, 32.1% hirsutism, and 45.3% had acne. The age at menarche was delayed in the T1DM group compared to controls (12.7 +/- 1.3 vs. 12.0 +/- 1.0 years; P = .004), while no difference was observed with the polycystic ovary syndrome (PCOS) group (12.4 +/- 1.2 years). There were no differences in total testosterone (0.43 +/- 0.14 ng/mL vs. 039 +/- 0.14 ng/mL; P>.05), dehydroepi- androsterone sulfate (DHEA-S) (269 +/- 112 mu g/dL vs. 238 +/- 106 mu g/dt,; P>.05) or Delta 4-androstenedione (2.4 +/- 1.3 ng/mL vs. 1.9 +/- 0.5 ng/mL; P>.05) concentrations between T1DM and controls. However, patients with T1DM had lower sex hormone binding globulin (SHBG) concentrations than controls (61 +/- 17 nmol/L, vs. 83 +/- 18.1 nmol/L; P = .001), which were even lower in the PCOS group (39.5 +/- 12.9 nmol/L; P = .001 compared with T1DM). The free androgen index (FAI) was higher in the PCOS group compared with both other groups (T1DM vs. PCOS vs. controls: 2.53 +/- 0.54 vs. 7.88 +/- 1.21 vs. 1.6 +/- 0.68; P<.001). FAI was higher in patients with T1DM compared to controls as well (P = .038). There was no difference in DHEA-S concentrations between T1DM and PCOS patients (269 +/- 112 mu g/dt, vs. 297 +/- 100 mu g/dL; P>.05). Conclusion: Menstrual disorders and androgen-related traits in young women with T1DM may be attributed to an increase in androgen bioavailability due to decreased SHBG concentrations