ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Seed germination and dormancy traits of forbs and shrubs important for restoration of North American dryland ecosystems

© 2018 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands In degraded dryland systems, native plant community re-establishment following disturbance is almost exclusively carried out using seeds, but these efforts commonly fail. Much of this failure can be attributed to the limited understanding of seed dormancy and germination traits. We undertook a systematic classification of seed dormancy of 26 species of annual and perennial forbs and shrubs that represent key, dominant genera used in restoration of the Great Basin ecosystem in the western United States. We examined germination across a wide thermal profile to depict species-specific characteristics and assessed the potential of gibberellic acid (GA3) and karrikinolide (KAR1) to expand the thermal germination envelope of fresh seeds. Of the tested species, 81% produce seeds that are dormant at maturity. The largest proportion (62%) exhibited physiological (PD), followed by physical (PY, 8%), combinational (PY + PD, 8%) and morphophysiological (MPD, 4%) dormancy classes. The effects of chemical stimulants were temperature- and species-mediated. In general, mean germination across the thermal profile was improved by GA3 and KAR1 for 11 and five species, respectively. We detected a strong germination response to temperature in freshly collected seeds of 20 species. Temperatures below 10 °C limited the germination of all except Agoseris heterophylla, suggesting that in their dormant state, the majority of these species are thermally restricted. Our findings demonstrate the utility of dormancy classification as a foundation for understanding the critical regenerative traits in these ecologically important species and highlight its importance in restoration planning

The vesicular monoamine transporter (VMAT-2) inhibitor tetrabenazine induces tremulous jaw movements in rodents: Implications for pharmacological models of parkinsonian tremor

Tetrabenazine (TBZ) is a reversible inhibitor of vesicular monoamine storage that is used to treat Huntington’s disease. TBZ preferentially depletes striatal dopamine (DA), and patients being treated with TBZ often experience parkinsonian side effects. The present studies were conducted to investigate the ability of TBZ to induce tremulous jaw movements (TJMs), which are a rodent model of parkinsonian tremor, and to determine if interference with adenosine A2A receptor transmission can attenuate TJMs and other motor effects of TBZ. In rats, TBZ (0.25–2.0 mg/kg) significantly induced TJMs, which primarily occurred in the 3.0–7.5-Hz frequency range. The adenosine A2A antagonist MSX-3 (1.25–10.0 mg/kg) significantly attenuated the TJMs induced by 2.0 mg/kg TBZ in rats, and also significantly reduced the display of catalepsy and locomotor suppression induced by TBZ. In mice, TBZ (2.5–10.0 mg/kg) dose dependently induced TJMs, and adenosine A2A receptor knockout mice showed significantly fewer TJMs compared to wild-type controls. MSX-3 (2.5–10.0 mg/kg) also significantly reduced TBZ-induced TJMs in CD1 mice. To provide a cellular marker of these pharmacological conditions, we examined c-Fos expression in the ventrolateral neostriatum (VLS). TBZ (2.0 mg/kg) significantly increased the number of c-Fos-positive cells in the VLS, which is indicative of reduced DA D2 receptor transmission, and 10.0 mg/kg MSX-3 significantly attenuated the TBZ-induced c-Fos expression. These results indicate that TBZ induces tremor as measured by the TJM model, and that pharmacological antagonism and genetic deletion of adenosine A2A receptors are capable of attenuating this oral tremor