MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.

Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort

Neural Network Development in Late Adolescents during Observation of Risk-Taking Action

Emotional maturity and social awareness are important for adolescents, particularly college students beginning to face the challenges and risks of the adult world. However, there has been relatively little research into personality maturation and psychological development during late adolescence and the neural changes underlying this development. We investigated the correlation between psychological properties (neuroticism, extraversion, anxiety, and depression) and age among late adolescents (n = 25, from 18 years and 1 month to 22 years and 8 months). The results revealed that late adolescents became less neurotic, less anxious, less depressive and more extraverted as they aged. Participants then observed video clips depicting hand movements with and without a risk of harm (risk-taking or safe actions) during functional magnetic resonance imaging (fMRI). The results revealed that risk-taking actions elicited significantly stronger activation in the bilateral inferior parietal lobule, temporal visual regions (superior/middle temporal areas), and parieto-occipital visual areas (cuneus, middle occipital gyri, precuneus). We found positive correlations of age and extraversion with neural activation in the insula, middle temporal gyrus, lingual gyrus, and precuneus. We also found a negative correlation of age and anxiety with activation in the angular gyrus, precentral gyrus, and red nucleus/substantia nigra. Moreover, we found that insula activation mediated the relationship between age and extraversion. Overall, our results indicate that late adolescents become less anxious and more extraverted with age, a process involving functional neural changes in brain networks related to social cognition and emotional processing. The possible neural mechanisms of psychological and social maturation during late adolescence are discussed

The Digital Fish Library: Using MRI to Digitize, Database, and Document the Morphological Diversity of Fish

Museum fish collections possess a wealth of anatomical and morphological data that are essential for documenting and understanding biodiversity. Obtaining access to specimens for research, however, is not always practical and frequently conflicts with the need to maintain the physical integrity of specimens and the collection as a whole. Non-invasive three-dimensional (3D) digital imaging therefore serves a critical role in facilitating the digitization of these specimens for anatomical and morphological analysis as well as facilitating an efficient method for online storage and sharing of this imaging data. Here we describe the development of the Digital Fish Library (DFL, http://www.digitalfishlibrary.org), an online digital archive of high-resolution, high-contrast, magnetic resonance imaging (MRI) scans of the soft tissue anatomy of an array of fishes preserved in the Marine Vertebrate Collection of Scripps Institution of Oceanography. We have imaged and uploaded MRI data for over 300 marine and freshwater species, developed a data archival and retrieval system with a web-based image analysis and visualization tool, and integrated these into the public DFL website to disseminate data and associated metadata freely over the web. We show that MRI is a rapid and powerful method for accurately depicting the in-situ soft-tissue anatomy of preserved fishes in sufficient detail for large-scale comparative digital morphology. However these 3D volumetric data require a sophisticated computational and archival infrastructure in order to be broadly accessible to researchers and educators

Increased airway mucins after cardiopulmonary bypass associated with postoperative respiratory complications in children

AbstractObjectiveAirway mucins may play an important role in the mechanism of respiratory complications after cardiopulmonary bypass in infants and children. Our aim was to measure airway mucin levels before and after cardiopulmonary bypass and to determine whether changes in mucin levels were associated with the development of respiratory complications.MethodsAirway glycoprotein and mucins (MUC5AC, MUC5B, and MUC2) in serial small-volume airway lavage samples from 39 young children who underwent cardiac operations with cardiopulmonary bypass were measured by slot-blot assay with specific antimucin peptide antibodies. The relationship between mucin changes and post–cardiopulmonary bypass respiratory complications was investigated. Airway lavage samples were also collected from 11 children before and after operation without cardiopulmonary bypass, and changes in mucin levels were compared with those in subjects who underwent cardiopulmonary bypass. Airway lavage sample DNA was also measured to investigate the relationship between mucin changes and lung injury.ResultsGlycoprotein, MUC5AC, and MUC5B levels were significantly increased after cardiopulmonary bypass (P < .001) whereas MUC2 level was not. Children with respiratory complications showed significantly higher glycoprotein and MUC5AC levels than did children without respiratory complications before and after cardiopulmonary bypass (P < .05). Increase of total mucin (MUC5AC, MUC5B, and MUC2) during cardiopulmonary bypass showed positive correlation with DNA increase during cardiopulmonary bypass (r = 0.73), Paco2 (r = 0.62) and alveolar-arterial oxygen difference (r = 0.55) immediately after cardiopulmonary bypass. Increase of total mucin was associated with postoperative respiratory complications and their severity. There were no significant changes detected in airway mucin during operations without cardiopulmonary bypass.ConclusionsAirway mucins were increased during cardiopulmonary bypass, and this increase was associated with markers of lung injury after cardiopulmonary bypass and with the development of postoperative respiratory complications

A severe asthma disease signature from gene expression profiling of eripheral blood from UBIOPRED cohorts

Rationale: Stratification of asthma at the molecular level, especially using accessible biospecimens, could greatly enable patient selection for targeted therapy. Objectives: To determine the value of blood to identify transcriptional differences between clinically defined asthmatic and non-asthmatic groups, identify potential patient subgroups based on gene expression, and explore biological pathways associated with identified differences. Methods: Transcriptomics profiles were generated by microarray analysis of blood from 610 asthmatic and control participants in U-BIOPRED. Differentially expressed genes (DEGs) were identified by ANOVA, including covariates for RNA quality, gender, and clinical site, and Ingenuity Pathway Analysis was applied. Patient subgroups based on DEGs were created by hierarchical clustering and topological data analysis. Measurements and Main Results: 1693 genes were differentially expressed between severe asthmatics and non-asthmatics. The differences to non-asthmatics in non-smoking severe and mild/moderate asthmatics were significantly related (r=0.76), with a larger effect size in the severe asthmatics. The majority, but not all, differences were explained by differences in circulating immune cell populations. Pathway analysis showed an increase in chemotaxis, migration, and myeloid cell trafficking in severe asthmatics, decreased B lymphocyte development and hematopoietic progenitor cells and lymphoid organ hypoplasia. Cluster analysis of DEGs created subgroups among the severe asthmatics that differed in molecular responses to oral corticosteroids. Conclusions: Blood gene expression differences between clinically defined subgroups of asthmatics and non-asthmatic individuals as well as subgroups of severe asthma defined by transcript profiles show the value of blood in stratifying asthma patients and identifying molecular pathways for further study