GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function : a report from the COGENT consortium

CORRIGENDUM Molecular Psychiatry (2017) 22, 1651–1652 http://www.nature.com/articles/mp2017197.pdfThe complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (similar to 8M single-nucleotide polymorphisms (SNP) with minor allele frequency >= 1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (PPeer reviewe

MKS3/TMEM67 mutations are a major cause of COACH syndrome, a joubert syndrome related disorder with liver involvement

The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/ aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the “molar tooth sign”, a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14 COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs

Histology of the Pharyngeal Constrictor Muscle in 22q11.2 Deletion Syndrome and Non-Syndromic Children with Velopharyngeal Insufficiency

Plastic surgeons aim to correct velopharyngeal insufficiency manifest by hypernasal speech with a velopharyngoplasty. The functional outcome has been reported to be worse in patients with 22q11.2 deletion syndrome than in patients without the syndrome. A possible explanation is the hypotonia that is often present as part of the syndrome. To confirm a myogenic component of the etiology of velopharyngeal insufficiency in children with 22q11.2 deletion syndrome, specimens of the pharyngeal constrictor muscle were taken from children with and without the syndrome. Histologic properties were compared between the groups. Specimens from the two groups did not differ regarding the presence of increased perimysial or endomysial space, fiber grouping by size or type, internalized nuclei, the percentage type I fibers, or the diameters of type I and type II fibers. In conclusion, a myogenic component of the etiology of velopharyngeal insufficiency in children with 22q11.2 deletion syndrome could not be confirmed

The dipole moments of the excited states of FeC

With the purpose of comparing expectation dipole moment values 〈μ〉 with finite-field obtained dipole moments μ FF, we recalculated by the finite-field method previously reported 〈μ〉 values of 38 excited states of FeC. In most of the cases μ FF is significantly larger than 〈μ〉.© 2005 American Institute of Physics

Metallocene-Naphthalimide Derivatives: The Effect of Geometry, DFT Methodology, and Transition Metals on Absorption Spectra

In the present paper, the photophysical properties of metallocene-4-amino-1,8-naphthalimide-piperazine molecules (1-M2+), as well as their oxidized and protonated derivatives (1−M3+, 1-M2+-H+, and 1-M3+-H+), where M = Fe, Co, and Ni, were studied via DFT and TD-DFT, employing three functionals, i.e., PBE0, TPSSh, and wB97XD. The effect of the substitution of the transition metal M on their oxidation state, and/or the protonation of the molecules, was investigated. The present calculated systems have not been investigated before and, except for the data regarding their photophysical properties, the present study provides important information regarding the effect of geometry and of DFT methodology on absorption spectra. It was found that small differences in geometry, specifically in the geometry of N atoms, reflect significant differences in absorption spectra. The common differences in spectra due to the use of different functionals can be significantly increased when the functionals predict minima even with small geometry differences. For most of the calculated molecules, the main absorption peaks in visible and near-UV areas correspond mainly to charge transfer excitations. The Fe complexes present larger oxidation energies at 5.4 eV, whereas Co and Ni complexes have smaller ones, at about 3.5 eV. There are many intense UV absorption peaks with excitation energies similar to their oxidation energies, showing that the emission from these excited states can be antagonistic to their oxidation. Regarding the use of functionals, the inclusion of dispersion corrections does not affect the geometry, and consequently the absorption spectra, of the present calculated molecular systems. For certain applications, where there is a need for a redox molecular system including metallocene, the oxidation energies could be lowered significantly, to about 40%, with the replacement of the iron with cobalt or nickel. Finally, the present molecular system, using cobalt as the transition metal, has the potential to be used as a sensor. © 2023 by the authors

First-principles investigation of the boron and aluminum carbides BC and AlC and their anions BC- and AlC-

Using ab initio multireference methods and large correlation consistent basis sets, we have investigated the ground electronic structure of the carbides BC and AlC, the ground and the first two excited states of the corresponding anions, BC- and AlC-, and the ground (linear) structures of the hydrides H-BC and H-AlC. By employing a series of increasing size basis sets for the BC molecule, i.e., cc-pV/iZ, aug-cc-pVnZ, cc-pCVnZ, and aug-cc-pCVnZ, n = 2, 3, 4, and 5, we have examined the convergence of its properties as a function of n. For both the neutral diatomic species and their anions we have obtained full potential energy curves, bond distances (re), dissociation energies (De), and the usual spectroscopic constants. For the BC molecule, our best re and De values are re = 1.4911 Å and De = 102.2 kcal/mol in excellent agreement with experimental results. In the AlC case the calculated De = 77.13 kcal/mol is at least 12 kcal/mol higher than the experimental number. No experimental or theoretical data exist in the literature for the anion BC-. For this system we obtain re = 1.4445 Å and De = 118.67 kcal/mol; the corresponding values of the AlC- species are re = 1.8945 Å and De = 77.16 kcal/mol. © 2001 American Chemical Society

The electronic structure of ScAl+. Ground and low-lying excited states

Using semiquantitative basis sets and ab initio multireference methods, we have investigated the electronic structure of scandium aluminide cation, ScAl+. In addition to the ground state (X2Δ), we have constructed potential energy curves for 20 more states spanning an energy range of no more than 1.5 eV. The first three states, X2Δ, 12∏, and 22∑+, are practically degenerate within the accuracy of our calculations. They have similar binding modes and a binding energy of about 30 kcal/mol with respect to their adiabatic fragments Sc(2D) + A1+(1S). The rest of the states correlate to Sc+(3D or 3F) + Al(2P). For all states we report bond lengths, dissociation energies, harmonic frequencies, Mulliken charges, and energy gaps. © 2000 American Chemical Society

Quadruple Bonding in the Ground and Low-Lying Excited States of the Diatomic Molecules TcN, RuC, RhB, and PdBe

Multiple bonds between atoms are one of the most fundamental aspects of chemistry. Double and triple bonds are quite common, while quadruple bonds are a true oddity and very rare for the main group elements. Identifying molecules containing quadruple bonds is very important and, even more so, determining the necessary requirements for the existence of such bonds. Here we present high-level theoretical calculations on the isoelectronic MX molecules, i.e., TcN, RuC, RhB, and PdBe, showing that such a quadruple bond with main group elements is not that uncommon. We found that quadruple bonds are formed in their ground states X3Δ(TcN) and χ1ς+ (RuC, RhB, and PdBe) and in the two lowest excited states of TcN (1ς+, 1Δ), RuC (1,3Δ), and RhB (1,3Δ). The quadruple bonds consist of two πand two σ bonds: (4dxz-2px)2, (4dyz-2py)2, (4dz2-2pz)2, and 5s0 → 2s2 (1ς+) or 5pz0→2s2 (1,3Δ). Bond lengths, dissociation energies, dipole moments, spectroscopic parameters, and relative energy ordering of the states were calculated via multireference and coupled cluster methodology using the aug-cc-pV5ZX(-PP)M basis sets. We study how the atomic states involved and how the gradual transition from covalent to dative bond, from TcN to PdBe, influence all of the calculated data, such as bond dissociation energies, bond lengths, and relative energy ordering of the states. Finally, we report the requirements for the occurrence of such bonds in molecular systems. All Be, B, C, and N atoms combining with the appropriate second-row transition metal can form quadruple bonds, while they cannot form such bonds with the first-row transition metals. © 2020 American Chemical Society