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Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the Enhancing Neuroimaging Genetics through Meta-Analysis for TS (ENIGMA-TS) working group. The ENIGMA-TS working group is an international collaborative effort bringing together a large network of investigators who aim to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with TS genomic data, as well as equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and the identification of biomarkers that could help inform improved clinical practice.
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Importance of favourable non-covalent contacts in the stereoselective synthesis of tetrasubstituted chromanones
Automated transition state (TS) structure computations for a recently reported Pd-catalysed conjugated addition of arylboronic acids to 2-substituted chromones (D. Baek, H. Ryu, J. Y. Ryu, J. Lee, B. M. Stoltz and S. Hong, Chem. Sci. , 2020, 11 , 4602–4607) reveal unexpected conformations of the key stereodifferentiating benzyl group on the pyridine-dihydroisoquinoline (PyDHIQ) ligand. Detailed analysis shows that stereoselectivity is determined primarily by favourable non-covalent contacts between this benzyl group and the substrates, combined with torsional strain in the primary TS structure leading to the minor stereoisomer. This finding should inform further use and analysis of PyDHIQ and related ligands in other stereoselective transformations.
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- Award ID(s):
- 1665407
- PAR ID:
- 10341294
- Date Published:
- Journal Name:
- Organic Chemistry Frontiers
- Volume:
- 9
- Issue:
- 11
- ISSN:
- 2052-4129
- Page Range / eLocation ID:
- 3027 to 3033
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D2QO00090C
