Single vibronic level emission spectroscopic studies of the ground state energy levels and molecular structures of jet-cooled HGeBr, DGeBr, HGeI, and DGeI

Single vibronic level dispersed fluorescence spectra of jet-cooled HGeBr, DGeBr, HGeI, and DGeI have been obtained by laser excitation of selected bands of the à A″1-X̃ A′1 electronic transition. The measured ground state vibrational intervals were assigned and fitted to anharmonicity expressions, which allowed the harmonic frequencies to be determined for both isotopomers. In some cases, lack of a suitable range of emission data necessitated that some of the anharmonicity constants and vibrational frequencies be estimated from those of HGeCl∕DGeCl and the corresponding silylenes (HSiX). Harmonic force fields were obtained for both molecules, although only four of the six force constants could be determined. The ground state effective rotational constants and force field data were combined to calculate average (rz) and approximate equilibrium (rze) structures. For HGeBr rze(GeH)=1.593(9)Å, rze(GeBr)=2.325(21)Å, and the bond angle was fixed at our CCSD(T)/aug-cc-pVTZ ab initio value of 93.6°. For HGeI we obtained rze(GeH)=1.589(1)Å, rze(GeI)=2.525(5)Å, and bond angle=93.2°. Franck-Condon simulations of the emission spectra using ab initio Cartesian displacement coordinates reproduce the observed intensity distributions satisfactorily. The trends in structural parameters in the halogermylenes and halosilylenes can be readily understood based on the electronegativity of the halogen substituent. ACKNOWLEDGMENT

A bone grease processing station at the Mitchell Prehistoric Indian Village: archaeological evidence for the exploitation of bone fats

© Association for Environmental Archaeology 2015. Author's accepted manuscript version deposited in accordance with SHERPA RoMEO guidelines. The definitive version is available at http://www.maneyonline.com/doi/abs/10.1179/1749631414Y.0000000035.Recent excavations at the Mitchell Prehistoric Indian Village, an Initial Middle Missouri site in Mitchell, South Dakota have revealed a large, clay-lined feature filled with fractured and fragmented bison bones. Fracture and fragmentation analysis, along with taphonomic evidence, suggests that the bones preserved within the feature represent evidence of prehistoric bone marrow and bone grease exploitation. Further, the character of the feature suggests that it served as a bone grease processing station. Bone fat exploitation is an activity that is frequently cited as a causal explanation for the nature of many fractured and fragmented bone assemblages in prehistory, and zooarchaeological assemblages have frequently been studied as evidence of bone fat exploitation. The Mitchell example provides some of the first direct, in-situ archaeological evidence of a bone grease processing feature, and this interpretation is sustained by substantial analytical evidence suggesting bone fat exploitation. This new evidence provides a clearer concept of the nature of bone fat exploitation in prehistory as well as an indication of the scale and degree to which bone grease exploitation occurred at the Mitchell site. Finally, this research demonstrates the importance of careful zooarchaeological and taphonomic analysis for the interpretation of both artifactual remains as well as archaeological features

Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network

Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ∼16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E−13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E − 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs

Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits

Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p &lt; 5 × 10−9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies. Delineation of the genetic architecture of hematological traits in a multi-ethnic dataset allows identification of rare variants with strong effects specific to non-European populations and improved fine mapping of GWAS variants using the trans-ethnic approach

Large-scale exome-wide association analysis identifies loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases

White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3 UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases

Raman intensity de-enhancement in nontotally symmetric vibrations of copper(II) acetate by forbidden ligand-field transitions

The Raman spectrum of the binuclear transition metal complex copper(II) acetate monohydrate is examined with various excitation wavelengths in the spectral range 17 500 to 25 000 cm−1. Nontotally symmetric vibrations are predominant in the Raman spectrum, and the depolarized Raman bands observed at 320 and 948 cm−1 exhibit marked intensity de‐enhancement as the excitation wavelength approaches the dimer‐associated, Laporte‐forbidden ligand‐field transition at 26 500 cm−1. The intensity de‐enhancement observed for the nontotally symmetric vibrations of copper(II) acetate is in contrast to that observed for other centrosymmetric transition metal complexes studied thus far in which only the totally symmetric vibrations exhibit antiresonance effects. The excitation profiles are calculated for the Raman bands of copper(II) acetate using a model in which the scattering intensity arises from two terms Iα|Be+Bf|2, where Bf couples two charge‐transfer states at 35 000 and 40 000 cm−1 respectively, and Be couples the ligand‐field state to the charge‐transfer state at 35 000 cm−1. The calculated profiles are in good agreement with those observed and predict that the system origin for the ligand‐field transition is located near 21 000 cm−1

Calculation of molecular polarizabilities using a semiclassical Slater‐type orbital‐point dipole interaction (STOPDI) model

The point dipole interaction model for molecular polarizability proposed by Applequist, Carl, and Fung [J. Am. Chem. Soc. 94, 2952 (1972)] is modified by replacing the point dipole interaction tensor with a descaled distributed charge interaction tensor. Our procedure is based on the descaled tensor algorithm proposed by Thole [Chem. Phys. 59, 341 (1981)] and uses a Slater‐type orbital (STO) function to represent the charge distribution. The resulting STOPDI formalism calculates mean molecular polarizabilities and the components of the molecular polarizabilities with errors comparable to experimental uncertainty. Furthermore, these procedures require only one optimized parameter per atom, the average atomic polarizability. The formalism is invariant to coordinate transformations and avoids the discontinuities and/or false resonances that are characteristic of previous classical and semiclassical formalisms. The STOPDI algorithm requires less parameterization and computation time than the anisotropic atom point dipole interaction (AAPDI) model of Birge [J. Chem. Phys. 72, 5312 (1980)] and is more reliable for the calculation of polarizability derivatives and Raman cross sections. We demonstrate, however, that none of the above formalisms are reliable for calculating absolute Raman cross sections for normal modes involving significant bond stretching components. This is an inherent limitation of any formalism which does not explicitly account for electron density redistribution accompanying changes in the internuclear distances of covalently bonded atoms