Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target

This review presents detailed information about the structure of triplet repeat RNA and addresses the simple sequence repeats of normal and expanded lengths in the context of the physiological and pathogenic roles played in human cells. First, we discuss the occurrence and frequency of various trinucleotide repeats in transcripts and classify them according to the propensity to form RNA structures of different architectures and stabilities. We show that repeats capable of forming hairpin structures are overrepresented in exons, which implies that they may have important functions. We further describe long triplet repeat RNA as a pathogenic agent by presenting human neurological diseases caused by triplet repeat expansions in which mutant RNA gains a toxic function. Prominent examples of these diseases include myotonic dystrophy type 1 and fragile X-associated tremor ataxia syndrome, which are triggered by mutant CUG and CGG repeats, respectively. In addition, we discuss RNA-mediated pathogenesis in polyglutamine disorders such as Huntington's disease and spinocerebellar ataxia type 3, in which expanded CAG repeats may act as an auxiliary toxic agent. Finally, triplet repeat RNA is presented as a therapeutic target. We describe various concepts and approaches aimed at the selective inhibition of mutant transcript activity in experimental therapies developed for repeat-associated diseases

Polygenic scores and onset of major mood or psychotic disorders among offspring of affected parents

Objective: Family history is an established risk factor for mental illness. The authors sought to investigate whether polygenic scores (PGSs) can complement family history to improve identification of risk for major mood and psychotic disorders. Methods: Eight cohorts were combined to create a sample of 1,884 participants ages 2–36 years, including 1,339 offspring of parents with mood or psychotic disorders, who were prospectively assessed with diagnostic interviews over an average of 5.1 years. PGSs were constructed for depression, bipolar disorder, anxiety, attention deficit hyperactivity disorder (ADHD), schizophrenia, neuroticism, subjective well-being, p factor, and height (as a negative control). Cox regression was used to test associations between PGSs, family history of major mental illness, and onsets of major mood and psychotic disorders. Results: There were 435 onsets of major mood and psychotic disorders across follow-up. PGSs for neuroticism (hazard ratio=1.23, 95% CI=1.12–1.36), schizophrenia (hazard ratio=1.15, 95% CI=1.04–1.26), depression (hazard ratio=1.11, 95% CI=1.01–1.22), ADHD (hazard ratio=1.10, 95% CI=1.00–1.21), subjective well-being (hazard ratio=0.90, 95% CI=0.82–0.99), and p factor (hazard ratio=1.14, 95% CI=1.04–1.26) were associated with onsets. After controlling for family history, neuroticism PGS remained significantly positively associated (hazard ratio=1.19, 95% CI=1.08–1.31) and subjective well-being PGS remained significantly negatively associated (hazard ratio=0.89, 95% CI=0.81–0.98) with onsets. Conclusions: Neuroticism and subjective well-being PGSs capture risk of major mood and psychotic disorders that is independent of family history, whereas PGSs for psychiatric illness provide limited predictive power when family history is known. Neuroticism and subjective well-being PGSs may complement family history in the early identification of persons at elevated risk

Seasonally resolved Mid-Holocene paleoclimate records derived from fossil giant clam shells (Tridacna squamoza) a calibration study and contribution to a global coral and bivalve database.

International audienceFossil shells of marine bivalves such as giant Tridacna provide information on past environments with seasonal resolutions. Similarly to corals, changes in mean seasonal cycles and inter-annual variability can be reconstructed by sequentially analyzing the annual layers of calcium carbonate. Previous inter-comparison studies conducted on modern material have shown that seasonally resolved records derived from marine bivalves (Tridacna gigas) and corals (Porites) provide similar information. This step has been necessary in order to combine these data sets into global databases. In this study, we have conducted a new calibration study of modern Tridacna squamosa which have been collected in several localities around Indonesia. Stable isotope (del-18O) and trace element profiles (Mg/Ca, Ba/Ca) have been measured and compared to local hydrology : sea surface temperature, rainfall and productivity. Mg/Ca and SST exhibit a clear linear relationship with similar equations regardless of the area of sampling. Additionally, comparison of measured and estimated del-18O confirm that this species precipitates their shells in isotopic equilibrium. The results from the calibration experiments are used to compare modern and fossil samples collected from Belitung Island located in the heart of the Java Sea. Our study shows that the mid-Holocene period, around 6ka, was slightly colder (mean temperature difference was 1°C) and lower salinity compared to modern conditions. These results are compared to model studies and other coral based data collected from locations further North in the South China Sea which show a northward displacement of the Intertropical Convergence zone during this period increasing rainfall rates over land and reducing precipitation in the Southern region of the South China Sea. We will finally illustrate how these data will be integrated in a global data base that is being compiled for the Holocene period and can serve for future data - model inter-comparison studies

Mid-Holocene paleoclimate records derived from fossil giant clam shells (Tridacna squamoza) from the Java Sea

International audienceFossil shells of marine bivalves such as giant Tridacnaprovide information on past environments with seasonal resolutions. Similarly to corals, changes in mean seasonal cycles and inter-annual variability can be reconstructed by sequentially analyzing the annual layers of calcium carbonate. Previous inter-comparison studies conducted on modern material have shown that seasonally resolved records derived from marine bivalves (Tridacna gigas) and corals (Porites) provide similar information. This step has been necessary in order to combine these data sets into global databases. In this study, we have conducted a new calibration study of modern Tridacna squamosawhich have been collected in several localities around Indonesia. Stable isotope (del-18O) and trace element profiles (Mg/Ca, Ba/Ca) have been measured and compared to local hydrology : sea surface temperature, rainfall and productivity. Mg/Ca and SST exhibit a clear linear relationship with similar equations regardless of the area of sampling. Additionally, comparison of measured and estimated del-18O confirm that this species precipitates their shells in isotopic equilibrium. The results from the calibration experiments are used to compare modern and fossil samples collected from Belitung Island located in the heart of the Java Sea. Our study shows that the mid-Holocene period, around 6ka, was slightly colder (mean temperature difference was 1°C) and lower salinity compared to modern conditions. These results are compared to model studies and other coral based data collected from locations further North in the South China Sea which show a northward displacement of the Intertropical Convergence zone during this period increasing rainfall rates over land and reducing precipitation in the Southern region of the South China Sea. We will finally illustrate how these data will be integrated in a global data base that is being compiled for the Holocene period and can serve for future data - model inter-comparison studies

Effects of Self Regulation vs. External Regulation on the Factors and Symptoms of Academic Stress in Undergraduate Students

The SRL vs. ERL theory has shown that the combination of levels of student self-regulation and regulation from the teaching context produces linear effects on achievement emotions and coping strategies. However, a similar effect on stress factors and symptoms of university students has not yet been demonstrated. The aim of this study was to test this prediction. It was hypothesized that the level of student selfregulation (low/medium/high), in interaction with the level of external regulation from teaching (low/medium/high), would also produce a linear effect on stress factors and symptoms of university students. A total of 527 undergraduate students completed validated questionnaires about self-regulation, regulatory teaching, stress factors, and symptoms. Using an ex post facto design by selection, ANOVAs and MANOVAs (3 × 3; 5 × 1; 5 × 2) were carried out. The results confirmed that the level of self-regulation and the level of regulatory teaching jointly determined the level of stress factors and symptoms of university students. Once again, a five-level heuristic of possible combinations was configured to jointly determine university students’ level of academic stress. We concluded that the combination of different levels of student regulation and regulation from the teaching process jointly determines university students’ level of academic stress. The implications for university students’ emotional health, stress prevention, and well-being are established