GObar: a gene ontology based analysis and visualization tool for gene sets

BACKGROUND: Microarray experiments, as well as other genomic analyses, often result in large gene sets containing up to several hundred genes. The biological significance of such sets of genes is, usually, not readily apparent.Identification of the functions of the genes in the set can help highlight features of interest. The Gene Ontology Consortium 1 has annotated genes in several model organisms using a controlled vocabulary of terms and placed the terms on a Gene Ontology (GO), which comprises three disjoint hierarchies for Molecular functions, Biological processes and Cellular locations. The annotations can be used to identify functions that are enriched in the set, but this analysis can be misleading since the underlying distribution of genes among various functions is not uniform. For example, a large number of genes in a set might be kinases just because the genome contains many kinases. RESULTS: We use the Gene Ontology hierarchy and the annotations to pick significant functions and pathways by comparing the distribution of functions in a given gene list against the distribution of all the genes in the genome, using the hypergeometric distribution to assign probabilities. GObar is a web-based visualizer that implements this algorithm.The public website for GObar 2 can analyse gene lists from the yeast (S. cervisiae), fly (D. Melanogaster), mouse (M. musculus) and human (H. sapiens) genomes. It also allows visualization of the GO tree, as well as placement of a single gene on the GO hierarchy. We analyse a gene list from a genomic study of pre-mRNA splicing to demonstrate the utility of GObar. CONCLUSION: GObar is freely available as a web-based tool at http://katahdin.cshl.org:9331/GO2 and can help analyze and visualize gene lists from genomic analyses

Lightweight genome viewer: portable software for browsing genomics data in its chromosomal context

Lightweight genome viewer (lwgv) is a web-based tool for visualization of sequence annotations in their chromosomal context. It performs most of the functions of larger genome browsers, while relying on standard flat-file formats and bypassing the database needs of most visualization tools. Visualization as an aide to discovery requires display of novel data in conjunction with static annotations in their chromosomal context. With database-based systems, displaying dynamic results requires temporary tables that need to be tracked for removal

RNAi Codex: a portal/database for short-hairpin RNA (shRNA) gene-silencing constructs

Use of RNA interference (RNAi) in forward genetic screens is proliferating. Currently, short-interfering RNAs (siRNAs) and short-hairpin RNAs (shRNAs) are being used to silence genes to tease out functional information. It is becoming easier to harness RNAi to silence specific genes, owing to the development of libraries of readymade shRNA and siRNA gene-silencing constructs by using a variety of sources. RNAi Codex, which consists of a database of shRNA related information and an associated website, has been developed as a portal for publicly available shRNA resources and is accessible at . RNAi Codex currently holds data from the Hannon–Elledge shRNA library and allows the use of biologist-friendly gene names to access information on shRNA constructs that can silence the gene of interest. It is designed to hold user-contributed annotations and publications for each construct, as and when such data become available. We will describe features of RNAi Codex and explain the use of the tool

Rotational and Vibrational Dynamics of Interstitial Molecular Hydrogen

The calculation of the hindered roton-phonon energy levels of a hydrogen molecule in a confining potential with different symmetries is systematized for the case when the rotational angular momentum $J$ is a good quantum number. One goal of this program is to interpret the energy-resolved neutron time of flight spectrum previously obtained for H$_{2}$C$_{60}$. This spectrum gives direct information on the energy level spectrum of H$_2$ molecules confined to the octahedral interstitial sites of solid C$_{60}$. We treat this problem of coupled translational and orientational degrees of freedom a) by construction of an effective Hamiltonian to describe the splitting of the manifold of states characterized by a given value of $J$ and having a fixed total number of phonon excitations, b) by numerical solutions of the coupled translation-rotation problem on a discrete mesh of points in position space, and c) by a group theoretical symmetry analysis. Results obtained from these three different approaches are mutually consistent. The results of our calculations explain several hitherto uninterpreted aspects of the experimental observations, but show that a truly satisfactory orientational potential for the interaction of an H$_2$ molecule with a surrounding array of C atoms has not yet been developed.Comment: 53 pages, 9 figures, to appear in Phys. Rev B (in press). Phys. Rev. B (in press

A Magnetic Transition Probed by the Ce Ion in Square-Lattice Antiferromagnet CeMnAsO

We examined the magnetic properties of the square-lattice antiferromagnets CeMnAsO and LaMnAsO and their solid solutions La1-xCexMnAsO by resistivity, magnetic susceptibility, and heat capacity measurements below room temperature. A first-order phase transition is observed at 34.1 K, below which the ground-state doublet of the Ce ion splits by 3.53 meV. It is likely that Mn moments already ordered above room temperature are reoriented at the transition, as reported for related compounds, such as NdMnAsO and PrMnSbO. This transition generates a large internal magnetic field at the Ce site in spite of the fact that simple Heisenberg interactions should be cancelled out at the Ce site owing to geometrical frustration. The transition takes place at nearly the same temperature with the substitution of La for Ce up to 90%. The Ce moment does not undergo long-range order by itself, but is parasitically induced at the transition, serving as a good probe for detecting the magnetism of Mn spins in a square lattice.Comment: 11 pages, 5 figures, to be published in J. Phys. Soc. Jp

Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex

PIWI proteins use guide piRNAs to repress selfish genomic elements, protecting the genomic integrity of gametes and ensuring the fertility of animal species. Efficient transposon repression depends on amplification of piRNA guides in the ping-pong cycle, which in Drosophila entails tight cooperation between two PIWI proteins, Aub and Ago3. Here we show that post-translational modification, symmetric dimethylarginine (sDMA), of Aub is essential for piRNA biogenesis, transposon silencing and fertility. Methylation is triggered by loading of a piRNA guide into Aub, which exposes its unstructured N-terminal region to the PRMT5 methylosome complex. Thus, sDMA modification is a signal that Aub is loaded with piRNA guide. Amplification of piRNA in the ping-pong cycle requires assembly of a tertiary complex scaffolded by Krimper, which simultaneously binds the N-terminal regions of Aub and Ago3. To promote generation of new piRNA, Krimper uses its two Tudor domains to bind Aub and Ago3 in opposite modification and piRNA-loading states. Our results reveal that post-translational modifications in unstructured regions of PIWI proteins and their binding by Tudor domains that are capable of discriminating between modification states is essential for piRNA biogenesis and silencing

Field-Induced Uniform Antiferromagnetic Order Associated with Superconductivity in Pr1−x_{1-x}LaCex_{x}CuO4−δ_{4-\delta}

Strong correlation between field-induced antiferromagnetic (AF) order and superconductivity is demonstrated for an electron-doped cuprate superconductor, Pr$_{1-x}$LaCe$_{x}$CuO$_{4-\delta}$ (PLCCO). In addition to the specimen with $x=0.11$ (which is close to the AF phase boundary, $x\simeq0.10$), we show that the one with $x=0.15$ ($T_c\simeq16$ K at zero field) also exhibits the field-induced AF order with a reduced magnitude of the induced moment. The uniform muon Knight shift at a low magnetic field ($\sim10^2$ Oe) indicates that the AF order is not localized within the cores of flux lines, which is in a marked contrast with theoretical prediction for hole-doped cuprates. The presence of anomalous non-diagonal hyperfine coupling between muons and Pr ions is also demonstrated in detail.Comment: 8 pages, 5 figures, to be published in J. Phys. Soc. Jp

Effect of a magnetic field on the long-range magnetic order in insulating Nd2CuO4, nonsuperconducting and superconducting Nd1.85Ce0.15CuO4

We have measured the effect of a c-axis aligned magnetic field on the long-range magnetic order of insulating Nd2CuO4, as-grown nonsuperconducting and superconducting Nd1.85Ce0.15CuO4. On cooling from room temperature, Nd2CuO4 goes through a series of antiferromagnetic (AF) phase transitions with different noncollinear spin structures. In all phases of Nd2CuO4, we find that the applied c-axis field induces a canting of the AF order but does not alter the basic zero-field noncollinear spin structures. Similar behavior is also found in as-grown nonsuperconducting Nd1.85Ce0.15CuO4. These results contrast dramatically with those of superconducting Nd1.85Ce0.15CuO4, where a c-axis aligned magnetic field induces a static, anomalously conducting, long-range ordered AF state. We confirm that the annealing process necessary to make superconducting Nd1.85Ce0.15CuO4 also induces epitaxial, three-dimensional long-range ordered cubic (Nd,Ce)2O3 as an impurity phase. In addition, the annealing process makes a series of quasi two-dimensional superlattice reflections associated with lattice distortions of Nd1.85Ce0.15CuO4 in the CuO2 plane. While the application of a magnetic field will induce a net moment in the impurity phase, we determine its magnitude and eliminate this as a possibility for the observed magnetic field-induced effect in superconducting Nd1.85Ce0.15CuO4.Comment: 12 pages, 10 figures, to be published in Phys. Rev.

Tudor domain containing 7 (Tdrd7) is essential for dynamic ribonucleoprotein (RNP) remodeling of chromatoid bodies during spermatogenesis

In the male germline in mammals, chromatoid bodies, a specialized assembly of cytoplasmic ribonucleoprotein (RNP), are structurally evident during meiosis and haploidgenesis, but their developmental origin and regulation remain elusive. The tudor domain containing proteins constitute a conserved class of chromatoid body components. We show that tudor domain containing 7 (Tdrd7), the deficiency of which causes male sterility and age-related cataract (as well as glaucoma), is essential for haploid spermatid development and defines, in concert with Tdrd6, key biogenesis processes of chromatoid bodies. Single and double knockouts of Tdrd7 and Tdrd6 demonstrated that these spermiogenic tudor genes orchestrate developmental programs for ordered remodeling of chromatoid bodies, including the initial establishment, subsequent RNP fusion with ubiquitous processing bodies/GW bodies and later structural maintenance. Tdrd7 suppresses LINE1 retrotransposons independently of piwi-interacting RNA (piRNA) biogenesis wherein Tdrd1 and Tdrd9 operate, indicating that distinct Tdrd pathways act against retrotransposons in the male germline. Tdrd6, in contrast, does not affect retrotransposons but functions at a later stage of spermiogenesis when chromatoid bodies exhibit aggresome-like properties. Our results delineate that chromatoid bodies assemble as an integrated compartment incorporating both germline and ubiquitous features as spermatogenesis proceeds and that the conserved tudor family genes act asmaster regulators of this unique RNP remodeling,which is genetically linked to the male germline integrity in mammals