Circadian polymorphisms associated with affective disorders

<p>Abstract</p> <p>Background</p> <p>Clinical symptoms of affective disorders, their response to light treatment, and sensitivity to other circadian interventions indicate that the circadian system has a role in mood disorders. Possibly the mechanisms involve circadian seasonal and photoperiodic mechanisms. Since genetic susceptibilities contribute a strong component to affective disorders, we explored whether circadian gene polymorphisms were associated with affective disorders in four complementary studies.</p> <p>Methods</p> <p>Four groups of subjects were recruited from several sources: 1) bipolar proband-parent trios or sib-pair-parent nuclear families, 2) unrelated bipolar participants who had completed the BALM morningness-eveningness questionnaire, 3) sib pairs from the GenRed Project having at least one sib with early-onset recurrent unipolar depression, and 4) a sleep clinic patient group who frequently suffered from depression. Working mainly with the SNPlex assay system, from 2 to 198 polymorphisms in genes related to circadian function were genotyped in the participant groups. Associations with affective disorders were examined with TDT statistics for within-family comparisons. Quantitative trait associations were examined within the unrelated samples.</p> <p>Results</p> <p>In <it>NR1D1</it>, rs2314339 was associated with bipolar disorder (P = 0.0005). Among the unrelated bipolar participants, 3 SNPs in <it>PER3 </it>and <it>CSNK1E </it>were associated with the BALM score. A <it>PPARGC1B </it>coding SNP, rs7732671, was associated with affective disorder with nominal significance in bipolar family groups and independently in unipolar sib pairs. In <it>TEF</it>, rs738499 was associated with unipolar depression; in a replication study, rs738499 was also associated with the QIDS-SR depression scale in the sleep clinic patient sample.</p> <p>Conclusion</p> <p>Along with anti-manic effects of lithium and the antidepressant effects of bright light, these findings suggest that perturbations of the circadian gene network at several levels may influence mood disorders, perhaps ultimately through regulation of MAOA and its modulation of dopamine transmission. Twenty-three associations of circadian polymorphisms with affective symptoms met nominal significance criteria (P < 0.05), whereas 15 would be expected by chance, indicating that many represented false discoveries (Type II errors). Some evidence of replication has been gathered, but more studies are needed to ascertain if circadian gene polymorphisms contribute to susceptibility to affective disorders.</p

Proteins identification of wheat-rye translocation lines by MALDI-TOF-TOF mass spectrometry and ESI-QTOF/MS

OBJECTIVE: To examine the relationship between Timed Up and Go (TUG) performance, verbal executive function (EF) performance, and quality-of-life (QOL) measures in Parkinson's disease (PD). DESIGN: Cross-sectional. SETTING: Sixteen movement disorder centers from across the United States. PARTICIPANTS: Patients with PD (N=1964). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: TUG test, immediate and delayed 5-word recall, verbal fluency, PD QOL Questionnaire. RESULTS: TUG performance and verbal EF performance were significantly associated with, and predictors of, QOL measures, having the greatest association and predictability with the mobility domain of the QOL measures. CONCLUSIONS: The TUG test and verbal EF tests have QOL correlates, making the combined evaluation of mobility, cognitive, and QOL decline a potential examination tool to evaluate the sequelae of PD

BPS States, Refined Indices, and Quiver Invariants

For D=4 BPS state construction, counting, and wall-crossing thereof, quiver quantum mechanics offers two alternative approaches, the Coulomb phase and the Higgs phase, which sometimes produce inequivalent counting. The authors have proposed, in arXiv:1205.6511, two conjectures on the precise relationship between the two, with some supporting evidences. Higgs phase ground states are naturally divided into the Intrinsic Higgs sector, which is insensitive to wall-crossings and thus an invariant of quiver, plus a pulled-back ambient cohomology, conjectured to be an one-to-one image of Coulomb phase ground states. In this note, we show that these conjectures hold for all cyclic quivers with Abelian nodes, and further explore angular momentum and R-charge content of individual states. Along the way, we clarify how the protected spin character of BPS states should be computed in the Higgs phase, and further determine the entire Hodge structure of the Higgs phase cohomology. This shows that, while the Coulomb phase states are classified by angular momentum, the Intrinsic Higgs states are classified by R-symmetry.Comment: 51 pages, 5 figure

The K2K SciBar Detector

A new near detector, SciBar, for the K2K long-baseline neutrino oscillation expe riment was installed to improve the measurement of neutrino energy spectrum and to study neutrino interactions in the energy region around 1 GeV. SciBar is a 'fully active' tracking detector with fine segmentation consisting of plastic scintillator bars. The detector was constructed in summer 2003 and is taking data since October 2003. The basic design and initial performance is presented.Comment: 7 pages, 4figures, Contributed to Proceedings of the 10th Vienna Conference on Instrumentation, Vienna, February 16-21, 200

Single-Molecule Analysis Reveals the Kinetics and Physiological Relevance of MutL-ssDNA Binding

DNA binding by MutL homologs (MLH/PMS) during mismatch repair (MMR) has been considered based on biochemical and genetic studies. Bulk studies with MutL and its yeast homologs Mlh1-Pms1 have suggested an integral role for a single-stranded DNA (ssDNA) binding activity during MMR. We have developed single-molecule Förster resonance energy transfer (smFRET) and a single-molecule DNA flow-extension assays to examine MutL interaction with ssDNA in real time. The smFRET assay allowed us to observe MutL-ssDNA association and dissociation. We determined that MutL-ssDNA binding required ATP and was the greatest at ionic strength below 25 mM (KD = 29 nM) while it dramatically decreases above 100 mM (KD>2 µM). Single-molecule DNA flow-extension analysis suggests that multiple MutL proteins may bind ssDNA at low ionic strength but this activity does not enhance stability at elevated ionic strengths. These studies are consistent with the conclusion that a stable MutL-ssDNA interaction is unlikely to occur at physiological salt eliminating a number of MMR models. However, the activity may infer some related dynamic DNA transaction process during MMR

CA125/MUC16 Is Dispensable for Mouse Development and Reproduction

Cancer antigen 125 (CA125) is a blood biomarker that is routinely used to monitor the progression of human epithelial ovarian cancer (EOC) and is encoded by MUC16, a member of the mucin gene family. The biological function of CA125/MUC16 and its potential role in EOC are poorly understood. Here we report the targeted disruption of the of the Muc16 gene in the mouse. To generate Muc16 knockout mice, 6.0 kb was deleted that included the majority of exon 3 and a portion of intron 3 and replaced with a lacZ reporter cassette. Loss of Muc16 protein expression suggests that Muc16 homozygous mutant mice are null mutants. Muc16 homozygous mutant mice are viable, fertile, and develop normally. Histological analysis shows that Muc16 homozygous mutant tissues are normal. By the age of 1 year, Muc16 homozygous mutant mice appear normal. Downregulation of transcripts from another mucin gene (Muc1) was detected in the Muc16 homozygous mutant uterus. Lack of any prominent abnormal phenotype in these Muc16 knockout mice suggests that CA125/MUC16 is not required for normal development or reproduction. These knockout mice provide a unique platform for future studies to identify the role of CA125/MUC16 in organ homeostasis and ovarian cancer

Display of probability densities for data from a continuous distribution

Based on cumulative distribution functions, Fourier series expansion and Kolmogorov tests, we present a simple method to display probability densities for data drawn from a continuous distribution. It is often more efficient than using histograms.Comment: 5 pages, 4 figures, presented at Computer Simulation Studies XXIV, Athens, GA, 201

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm