Genes that are differentially expressed between schizophrenia patients and healthy controls may have key roles in the pathogenesis of schizophrenia. We analyzed two large-scale genome-wide expression ...studies, which examined changes in gene expression in schizophrenia patients and their matched controls. We found calcium/calmodulin (CAM)-dependent protein kinase kinase 2 (CAMKK2) is significantly downregulated in individuals with schizophrenia in both studies. To seek the potential genetic variants that may regulate the expression of CAMKK2, we investigated the association between single-nucleotide polymorphisms (SNPs) within CAMKK2 and the expression level of CAMKK2. We found one SNP, rs1063843, which is located in intron 17 of CAMKK2, is strongly associated with the expression level of CAMKK2 in human brains (P=1.1 × 10(-6)) and lymphoblastoid cell lines (the lowest P=8.4 × 10(-6)). We further investigated the association between rs1063843 and schizophrenia in multiple independent populations (a total of 130 623 subjects) and found rs1063843 is significantly associated with schizophrenia (P=5.17 × 10(-5)). Interestingly, we found the T allele of rs1063843, which is associated with lower expression level of CAMKK2, has a higher frequency in individuals with schizophrenia in all of the tested samples, suggesting rs1063843 may be a causal variant. We also found that rs1063843 is associated with cognitive function and personality in humans. In addition, protein-protein interaction (PPI) analysis revealed that CAMKK2 participates in a highly interconnected PPI network formed by top schizophrenia genes, which further supports the potential role of CAMKK2 in the pathogenesis of schizophrenia. Taken together, these converging lines of evidence strongly suggest that CAMKK2 may have pivotal roles in schizophrenia susceptibility.
Scholars' small knowledge of Alcaeus' Book 1 can give much more illumination to Horace Odes 1 than they currently permit it to, and vice versa. The publication and text of the works are discussed.
The baking properties of several genotypes of U.S. hard wheats grown in state nurseries for the Wheat Quality Council (WQC) were analyzed by the Hard Winter Wheat Quality Laboratory. Flours (250 mg) ...from each individual line and location were extracted three times with 50% 1-propanol (1 mL) for 5 min each. Samples were vortexed continually during extraction. This method was effective in removing most monomeric proteins. Negligible detectable protein was found in the third extract. Significant amounts of polymeric glutenin were also extracted. Pellets were oven-dried (130 degrees C) for 1 hr and analyzed for protein content using nitrogen combustion analysis. Protein remaining in the pellet consisted mainly of polymeric protein. The amount of gliadin and soluble polymeric protein could also be measured by separating the supernatant by size-exclusion chromatography. Good correlations between dough strength parameters and amounts of pellet protein and the relative amount of pellet protein (pellet protein/flour protein) were found for all samples. This procedure was simple and rapid, with the potential of analyzing large numbers of samples per day with good reproducibility
This article, which was substantively complete at the time of Professor Lyne's sad death, takes a close look at Horace Epodes 13. Lyne displays the complex intertextual and generic resonances of the ...poem, which is crossed between iambic and lyric ancestry. The poem also functions as a major structural element in the book of Epodes, since it appears to signal a closure which does not happen, and which is wittily picked up in the following poem's apology to Maecenas for the poet's inability to finish the book. This play with finishing, and with iambic books of 13 or 17 poems in length, alludes to Callimachus and his book of Iambi. The closural elements in Epode 13 resonate which similar closurality in Iambus XIII, and the continuation in Epodes 14–17 is Horace's reflection on the puzzle about whether Iambus XIII represents closure ‘followed by heterogeneous material filled out either by Callimachus himself or by a copyist or “false closure” followed by more Iambi’.
Sexual reproduction requires meiosis to produce haploid gametes, which in turn can fuse to regenerate a diploid organism. We have studied the transcriptional program that drives this developmental ...process in Schizosaccharomyces pombe using DNA microarrays. Here we show that hundreds of genes are regulated in successive waves of transcription that correlate with major biological events of meiosis and sporulation. Each wave is associated with specific promoter motifs. Clusters of neighboring genes (mostly close to telomeres) are co-expressed early in the process, which reflects a more global control of these genes. We find that two Atf-like transcription factors are essential for the expression of late genes and formation of spores, and identify dozens of potential Atf target genes. Comparison with the meiotic program of the distantly related Saccharomyces cerevisiae reveals an unexpectedly small shared meiotic transcriptome, suggesting that the transcriptional regulation of meiosis evolved independently in both species.
We explored transcriptional responses of the fission yeast Schizosaccharomyces pombe to various environmental stresses. DNA microarrays were used to characterize changes in expression profiles of all ...known and predicted genes in response to five stress conditions: oxidative stress caused by hydrogen peroxide, heavy metal stress caused by cadmium, heat shock caused by temperature increase to 39 degrees C, osmotic stress caused by sorbitol, and DNA damage caused by the alkylating agent methylmethane sulfonate. We define a core environmental stress response (CESR) common to all, or most, stresses. There was a substantial overlap between CESR genes of fission yeast and the genes of budding yeast that are stereotypically regulated during stress. CESR genes were controlled primarily by the stress-activated mitogen-activated protein kinase Sty1p and the transcription factor Atf1p. S. pombe also activated gene expression programs more specialized for a given stress or a subset of stresses. In general, these "stress-specific" responses were less dependent on the Sty1p mitogen-activated protein kinase pathway and may involve specific regulatory factors. Promoter motifs associated with some of the groups of coregulated genes were identified. We compare and contrast global regulation of stress genes in fission and budding yeasts and discuss evolutionary implications.
modMine: flexible access to modENCODE data Contrino, Sergio; Smith, Richard N; Butano, Daniela ...
Nucleic acids research,
01/2012, Letnik:
40, Številka:
D1
Journal Article
Recenzirano
Odprti dostop
In an effort to comprehensively characterize the functional elements within the genomes of the important model organisms Drosophila melanogaster and Caenorhabditis elegans, the NHGRI model organism ...Encyclopaedia of DNA Elements (modENCODE) consortium has generated an enormous library of genomic data along with detailed, structured information on all aspects of the experiments. The modMine database (http://intermine.modencode.org) described here has been built by the modENCODE Data Coordination Center to allow the broader research community to (i) search for and download data sets of interest among the thousands generated by modENCODE; (ii) access the data in an integrated form together with non-modENCODE data sets; and (iii) facilitate fine-grained analysis of the above data. The sophisticated search features are possible because of the collection of extensive experimental metadata by the consortium. Interfaces are provided to allow both biologists and bioinformaticians to exploit these rich modENCODE data sets now available via modMine.
Climactic moments in Shakespeare often suggest a need for proportionate physical gestures (such as embraces, or touches). Such movements are very carefully managed, and sometimes strikingly deferred. ...Close attention to the precise stagecraft and textual manoeuvres involved raises questions about how touches in his plays should be approached. From a variety of perspectives (especially John Bulwer's seventeenth-century manual of the rhetoric of hands, and the research of twentieth-and twenty-first century cognitive scientists into how we watch actions) suggestions emerge about the special affective processes pertaining to touches which are linked to, and sometimes encapsulate, intentions and emotions. These help illuminate Shakespearean dramaturgy, but they also reveal the kinds of knowledge and experiment arising in the plays themselves.
Lyne dates Propertius Book 1, Tibullus Book 1 and Propertius Books 2a and 2b. Some Tibullan responses to Propertius Book1 and some Propertian responses to Tibullus Book 1 are discussed also.
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