Although historically research findings about racial and ethnic issues were all too often used to support prevailing concepts of racial inferiority, in recent years racial and ethnic factors have ...frequently been ignored. However, current findings suggest that racial and ethnic differences exist in the symptom presentations of psychiatric disorders. Significant racial differences have been noted among proposed biological markers for various psychiatric disorders, such as serum creatinine phosphokinase, platelet serotonin, and HLA-A2. Racial and ethnic differences in response to psychotropic medication, such as higher blood levels found among Asians, affect dosage requirements and potential side effects. All of these developments underline the importance of considering ethnic and racial factors in psychiatric research.
About the Authors: Didier Y. R. Stainier * E-mail: didier.stainier@mpi-bn.mpg.de (DYRS); cmoens@fredhutch.org (CBM) Affiliation: Department of Developmental Genetics, Max Planck Institute for Heart ...and Lung Research, Bad Nauheim, Germany ORCID http://orcid.org/0000-0002-0382-0026 Erez Raz Affiliation: Institute of Cell Biology, ZBME, University of Münster, Münster, Germany ORCID http://orcid.org/0000-0002-6347-3302 Nathan D. Lawson Affiliation: Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America Stephen C. Ekker Affiliation: Mayo Clinic, Rochester, Minnesota, United States of America Rebecca D. Burdine Affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America Judith S. Eisen Affiliation: Institute of Neuroscience, University of Oregon, Eugene, Oregon, United States of America ORCID http://orcid.org/0000-0003-1229-1696 Philip W. Ingham Affiliations Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, The Living Systems Institute, University of Exeter, Exeter, United Kingdom Stefan Schulte-Merker Affiliation: Institute of Cardiovascular Organogenesis and Regeneration, WWU Münster, Faculty of Medicine, Münster, Germany Deborah Yelon Affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America Brant M. Weinstein Affiliation: Division of Developmental Biology, NICHD, NIH, Bethesda, Maryland, United States of America Mary C. Mullins Affiliation: Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America ORCID http://orcid.org/0000-0002-9979-1564 Stephen W. Wilson Affiliation: Department of Cell and Developmental Biology, University College London, London, United Kingdom ORCID http://orcid.org/0000-0002-8557-5940 Lalita Ramakrishnan Affiliation: Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom Sharon L. Amacher Affiliation: Departments of Molecular Genetics and Biological Chemistry and Pharmacology, Ohio State University, Columbus, Ohio, United States of America Stephan C. F. Neuhauss Affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland ORCID http://orcid.org/0000-0002-9615-480X Anming Meng Affiliation: School of Life Sciences, Tsinghua University, Beijing, China Naoki Mochizuki Affiliation: National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan ORCID http://orcid.org/0000-0002-3938-9602 Pertti Panula Affiliation: Department of Anatomy and Neuroscience Center, University of Helsinki, Helsinki, Finland Cecilia B. Moens * E-mail: didier.stainier@mpi-bn.mpg.de (DYRS); cmoens@fredhutch.org (CBM) Affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of AmericaCitation: Stainier DYR, Raz E, Lawson ND, Ekker SC, Burdine RD, Eisen JS, et al. Additionally, mutant alleles for many genes are now readily available through zebrafish community resource centers. ...MOs should be used alongside mutant(s) for the corresponding gene. ...a word of caution that previous publication of MOs is not a guarantee of their fidelity, particularly if a new phenotype is being described. ...we hope that these brief and mostly conceptual guidelines will assist scientists working with zebrafish as well as those assessing manuscripts and grant proposals based on experiments using zebrafish.
The widespread availability of programmable site-specific nucleases now enables targeted gene disruption in the zebrafish. In this study, we applied site-specific nucleases to generate zebrafish ...lines bearing individual mutations in more than 20 genes. We found that mutations in only a small proportion of genes caused defects in embryogenesis. Moreover, mutants for ten different genes failed to recapitulate published Morpholino-induced phenotypes (morphants). The absence of phenotypes in mutant embryos was not likely due to maternal effects or failure to eliminate gene function. Consistently, a comparison of published morphant defects with the Sanger Zebrafish Mutation Project revealed that approximately 80% of morphant phenotypes were not observed in mutant embryos, similar to our mutant collection. Based on these results, we suggest that mutant phenotypes become the standard metric to define gene function in zebrafish, after which Morpholinos that recapitulate respective phenotypes could be reliably applied for ancillary analyses.
•Site-specific nucleases used to generate a collection of zebrafish mutants•Most mutants displayed normal embryonic development•Most mutants failed to recapitulate published Morpholino phenotypes•Parallel informatics analysis suggests high false-positive rates for Morpholinos
Kok et al. report that their frameshift mutations seldom replicate published morphant phenotypes. Neither maternal effects nor failures to follow standard knockdown guidelines readily account for the discrepancy. While mutants may be slightly more prone to amelioration by long-term compensatory mechanisms, many morphant phenotypes are likely attributable to off-target effects.
A series of 2(
Z)-2-benzylidene-6,7-dihydroxybenzofuran-32H-ones was identified as potent inhibitors of bacterial chorismate synthase. The 2′-hydroxy-4′-pentoxy analogue
33 is a potent inhibitor of
...Streptococcus pneumoniae chorismate synthase.
We have synthesized a series of 2(
Z)-2-benzylidene-6,7-dihydroxybenzofuran-32H-ones. Inhibitory activity of
Streptococcus pneumoniae chorismate synthase is reported.
This randomized controlled trial compares the efficacy and safety of olanzapine vs haloperidol, as well as the quality of life of patients taking these drugs, in patients with bipolar mania.
The ...design consisted of 2 successive, 6-week, double-blind periods and compared flexible dosing of olanzapine (5-20 mg/d, n = 234) with haloperidol (3-15 mg/d, n = 219).
Rates of remission (Young-Mania Rating Scale score of < or =12 and 21-item Hamilton Rating Scale for Depression score of < or =8 at week 6) were similar for olanzapine- and haloperidol-treated patients (52.1% vs 46.1%, respectively; P =.15). For the subgroup of patients whose index episode did not include psychotic features, rates of remission were significantly greater for the olanzapine group compared with the haloperidol group (56.7% vs 41.6%, P =.04). Relapse into an affective episode (mania and/or depression) occurred in 13.1% and 14.8% of olanzapine- and haloperidol-treated patients, respectively (P =.56). Switch to depression occurred significantly more rapidly with haloperidol than with olanzapine when using survival analysis techniques (P =.04), and significantly more haloperidol-treated patients experienced worsening of extrapyramidal symptoms, as indicated by several measures. Weight gain was significantly greater in the olanzapine group compared with the haloperidol group (2.82 vs 0.02 kg, P<.001). The olanzapine group had significant improvement in quality of life on several dimensions compared with the haloperidol group.
These data suggest that olanzapine does not differ from haloperidol in achieving overall remission of bipolar mania. However, haloperidol carries a higher rate of extrapyramidal symptoms, whereas olanzapine is associated with weight gain.
Recent research and clinical experience has shown that African Americans may be at greater risk for inappropriate treatment. Such experiences can interact negatively with an existing distrust of the ...mental health system. Providers may show different prescribing patterns with racial and ethnic minorities: they may overuse antipsychotics, dispense higher dosages, and more commonly give involuntary treatment, which results in more side effects and a poorer outcome. Conversely, they may underuse other psychotropic medications, especially for anxiety and affective disorders, which are underdiagnosed in minorities. Recent research suggests that ethnic differences may exist in pharmacokinetics, and so different dosing strategies may be necessary. Not surprisingly African Americans in distress are more likely to seek initial treatment outside of the mental health system, seek treatment later in the course of the illness, complain more about side effects, and terminate treatment earlier. Cultural as well as socioeconomic factors must be considered. Newer pharmacological agents may be potentially more helpful for minorities because they are better tolerated, have better side effect profiles, and demonstrate better efficacy. However, African Americans have limited access to these agents. Education of providers and patients, policy changes in the public sector, wider implementation of research policies concerning inclusion of minorities, and different marketing strategies by pharmaceutical concerns are probably necessary to maximize pharmacotherapy of minorities.
We present constraints on the existence of weakly interacting massive particles (WIMPs) from an 11 kg d target exposure of the DAMIC experiment at the SNOLAB underground laboratory. The observed ...energy spectrum and spatial distribution of ionization events with electron-equivalent energies >200 eV_{ee} in the DAMIC CCDs are consistent with backgrounds from natural radioactivity. An excess of ionization events is observed above the analysis threshold of 50 eV_{ee}. While the origin of this low-energy excess requires further investigation, our data exclude spin-independent WIMP-nucleon scattering cross sections σ_{χ-n} as low as 3×10^{-41} cm^{2} for WIMPs with masses m_{χ} from 7 to 10 GeV c^{-2}. These results are the strongest constraints from a silicon target on the existence of WIMPs with m_{χ}<9 GeV c^{-2} and are directly relevant to any dark matter interpretation of the excess of nuclear-recoil events observed by the CDMS silicon experiment in 2013.
We report a genome-wide association study (GWAS) of major depressive disorder (MDD) in 1,221 cases from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 1,636 screened ...controls. No genome-wide evidence for association was detected. We also carried out a meta-analysis of three European-ancestry MDD GWAS datasets: STAR*D, Genetics of Recurrent Early-Onset Depression (GenRED) and the publicly-available Genetic Association Information Network MDD dataset (GAIN-MDD). These datasets, totaling 3,957 cases and 3,428 controls, were genotyped using four different platforms (Affymetrix 6.0, 5.0 and 500K, and Perlegen). For each of 2.4 million HapMap II SNPs, using genotyped data where available and imputed data otherwise, single-SNP association tests were carried out in each sample with correction for ancestry-informative principal components. The strongest evidence for association in the meta-analysis was observed for intronic SNPs in
ATP6V1B2
(P = 6.78 × 10
−7
),
SP4
(
P
= 7.68 × 10
−7
) and
GRM7
(
P
= 1.11 × 10
−6
). Additional exploratory analyses were carried out for a narrower phenotype (recurrent MDD with onset before age 31, N = 2,191 cases), and separately for males and females. Several of the best findings were supported primarily by evidence from narrow cases or from either males or females. Based on previous biological evidence, we consider
GRM7
a strong MDD candidate gene. Larger samples will be required to determine whether any common SNPs are significantly associated with MDD.
This work is Part 1 in a two part series that investigates the interfacial decomposition chemistry of pyr14TFSI and EMIMBF4 ionic liquids (IL) at Li metal interfaces. Here, the decomposition is ...probed primarily through ab initio molecular dynamics (AIMD) simulations. For single ion pairs adsorbed on a Li(100) surface, hybrid ion states are found to emerge about the Fermi level. Interestingly, these states have a significant contribution from both ions, which suggests that the cathodic (reductive) stability could in part be governed by the anions. Room temperature AIMD simulations reveal rapid decomposition of the TFSI anion initiated by C–S and/or S–N bond cleavage due to charge transfer from Li to the anion. The unusual phenomenon of reductive decomposition of the anion is supported by recent experimental reports. The reaction products observed included LiF, LiO, Li2F, Li2O, SO2, NSO2, NSO2CF3, etc., which are all in excellent agreement with the XPS results. Initial decomposition reactions for both cations and the BF4 anion were only observed in high temperature AIMD simulations. For bulk ILs interfaces with a Li(100) surface, interfacial decomposition reactions again result from charge transfer to the IL from the Li surface, in particular, to anions at the interfaces. The initial decomposition event at bulk interfaces is found to vary depending on the interface structure. The extensive computational analyses presented in this work provide valuable insights into the fundamental interfacial chemistry of ILs in contact with Li metal. In Part 2 of this series, we consider these results further by systematically examining ion reductive stability, the thermodynamics of decomposition, and kinetic limitations to decomposition using gas phase density functional theory (DFT) computations. Results from these studies can be used for further design of these, or perhaps other, ILs to obtain more stable solid electrolyte interface (SEI) layers to improve cycling in advanced battery chemistries.
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