Partially Quenched QCD with Non-Degenerate Dynamical Quarks

We discuss the importance of using partially quenched theories with three degenerate quarks for extrapolating to QCD, and present some relevant results from chiral perturbation theory.Comment: LATTICE99 talk. 3 pages, 2 figures. Uses epsf and espcrc2.st

Chiral perturbation theory for lattice QCD including O(a^2)

The O(a^2) contributions to the chiral effective Lagrangian for lattice QCD with Wilson fermions are constructed. The results are generalized to partially quenched QCD with Wilson fermions as well as to the "mixed'' lattice theory with Wilson sea quarks and Ginsparg-Wilson valence quarks.Comment: 3 pages, Lattice2003 (spectrum

Light hadron spectra and wave functions in quenched QCD with overlap quarks on a large lattice

A simulation of quenched QCD with the overlap Dirac operator has been completed using 100 Wilson gauge configurations at beta=6 on an 18^3x64 lattice. We present results for meson and baryon masses, meson final state "wave functions'' and other observables.Comment: 5 LaTeX pages (espcrc2.sty), 13 figures. Combined contributions by J.H., L.L. and C.R. at Lattice2004(spectrum), Fermilab, June 21-26, 200

ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia

Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing ChIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of ChIP-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http://encodeproject.org/ENCODE/) and modENCODE (http://www.modencode.org/) portals

An Evolutionary Conserved Role for Anaplastic Lymphoma Kinase in Behavioral Responses to Ethanol

Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk expression levels in the brains of recombinant inbred mice are negatively correlated with ethanol-induced ataxia and ethanol consumption. We therefore tested Alk gene knockout mice and found that they sedate longer in response to high doses of ethanol and consume more ethanol than wild-type mice. Finally, sequencing of human ALK led to the discovery of four polymorphisms associated with a low level of response to ethanol, an intermediate phenotype that is predictive of future alcohol use disorders (AUDs). These results suggest that Alk plays an evolutionary conserved role in ethanol-related behaviors. Moreover, ALK may be a novel candidate gene conferring risk for AUDs as well as a potential target for pharmacological intervention

Molecular effects of resistance elicitors from biological origin and their potential for crop protection

Plants contain a sophisticated innate immune network to prevent pathogenic microbes from gaining access to nutrients and from colonising internal structures. The first layer of inducible response is governed by the plant following the perception of microbe- or modified plant-derived molecules. As the perception of these molecules results in a plant response that can provide efficient resistance towards non-adapted pathogens they can also be described as ‘defence elicitors’. In compatible plant/microbe interactions, adapted microorganisms have means to avoid or disable this resistance response and promote virulence. However, this requires a detailed spatial and temporal response from the invading pathogens. In agricultural practice, treating plants with isolated defence elicitors in the absence of pathogens can promote plant resistance by uncoupling defence activation from the effects of pathogen virulence determinants. The plant responses to plant, bacterial, oomycete or fungal-derived elicitors are not, in all cases, universal and need elucidating prior to the application in agriculture. This review provides an overview of currently known elicitors of biological rather than synthetic origin and places their activity into a molecular context

Transcriptional Regulation by CHIP/LDB Complexes

It is increasingly clear that transcription factors play versatile roles in turning genes “on” or “off” depending on cellular context via the various transcription complexes they form. This poses a major challenge in unraveling combinatorial transcription complex codes. Here we use the powerful genetics of Drosophila combined with microarray and bioinformatics analyses to tackle this challenge. The nuclear adaptor CHIP/LDB is a major developmental regulator capable of forming tissue-specific transcription complexes with various types of transcription factors and cofactors, making it a valuable model to study the intricacies of gene regulation. To date only few CHIP/LDB complexes target genes have been identified, and possible tissue-dependent crosstalk between these complexes has not been rigorously explored. SSDP proteins protect CHIP/LDB complexes from proteasome dependent degradation and are rate-limiting cofactors for these complexes. By using mutations in SSDP, we identified 189 down-stream targets of CHIP/LDB and show that these genes are enriched for the binding sites of APTEROUS (AP) and PANNIER (PNR), two well studied transcription factors associated with CHIP/LDB complexes. We performed extensive genetic screens and identified target genes that genetically interact with components of CHIP/LDB complexes in directing the development of the wings (28 genes) and thoracic bristles (23 genes). Moreover, by in vivo RNAi silencing we uncovered novel roles for two of the target genes, xbp1 and Gs-alpha, in early development of these structures. Taken together, our results suggest that loss of SSDP disrupts the normal balance between the CHIP-AP and the CHIP-PNR transcription complexes, resulting in down-regulation of CHIP-AP target genes and the concomitant up-regulation of CHIP-PNR target genes. Understanding the combinatorial nature of transcription complexes as presented here is crucial to the study of transcription regulation of gene batteries required for development

A User's Guide to the Encyclopedia of DNA Elements (ENCODE)

The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome.National Human Genome Research Institute (U.S.)National Institutes of Health (U.S.