Ulysses - an application for the projection of molecular interactions across species

We developed Ulysses as a user-oriented system that uses a process called Interolog Analysis for the parallel analysis and display of protein interactions detected in various species. Ulysses was designed to perform such Interolog Analysis by the projection of model organism interaction data onto homologous human proteins, and thus serves as an accelerator for the analysis of uncharacterized human proteins. The relevance of projections was assessed and validated against published reference collections. All source code is freely available, and the Ulysses system can be accessed via a web interface .     

Pegasys: software for executing and integrating analyses of biological sequences

Background  

We present Pegasys – a flexible, modular and customizable software system that facilitates the execution and data integration from heterogeneous biological sequence analysis tools.     

A yield control approach to assess phytoavailability of Zn and Cu in irradiated,composted sewage sludges and composted manure in field experiments: I. Zinc

The threat of spreading diseases is a serious concern when organic wastes are applied to farmland. Irradiation and composting are effective methods to reduce pathogens. Field experiments were conducted to assess the influence of these pathogen-eliminating methods on plant availability of Zn in the wastes. Four organic wastes: digested and dewatered (DSS), irradiated (DISS), composted (DICSS) sewage sludge and composted livestock manure (CLM) were applied during two growing seasons at 10, 20, 30, and 40 t solids ha^–1 year^–1. Available N and K in the wastes were estimated and N and K fertilizers were added to the soil to equalize available N and K supply among treatments to avoid dilution of crop Zn concentration. A control treatment (CT) received fertilizers but no waste. Lettuce, snap beans and petunias were grown in 1990, and two cuts of lettuce were harvested in 1991. The influence of waste Zn application on crop Zn concentration was studied within approximately equal crop yields. Crop Zn concentration increased in all crops treated with DSS or DISS, and often reached a maximum at the 30 t ha^–1 rate of application, then slightly decreased at 40 t ha^–1. The response of crop Zn concentration to the amount of Zn applied in the wastes was best described by quadratic equations. Waste application also significantly increased soil Zn availability index, which was a function of DTPA (diethylenetriamine pentaacetic acid)-extractable soil Zn and soil pH. The index was highly correlated with crop Zn concentration. Although Zn concentration in DICSS was similar to those in DSS and DISS, Zn applied in DICSS did not increase crop Zn concentration or soil availability index. Composting reduced the availability of Zn. The similar concentrations of Zn in DSS and DISS in both years allowed the use of a paired t-test to determine the differences in crop Zn concentration caused by application of DSS and DISS. Zinc applied in DISS produced a higher Zn concentration in bean pods than Zn applied in DSS (t > T _0.05 at P < 0.02, df = 15), indicating that irradiation increased phytoavailability of Zn in the sludge. However, no similar effect was found in Zn concentrations in the two cuts of lettuce in 1991 or in soil Zn availability index.     

Vasoactivity of Rucaparib,a PARP-1 Inhibitor,is a Complex Process that Involves Myosin Light Chain Kinase,P2 Receptors,and PARP Itself

Therapeutic inhibition of poly(ADP-ribose) polymerase (PARP), as monotherapy or to supplement the potencies of other agents, is a promising strategy in cancer treatment. We previously reported that the first PARP inhibitor to enter clinical trial, rucaparib ({"type":"entrez-nucleotide","attrs":{"text":"AG014699","term_id":"3649917","term_text":"AG014699"}}AG014699), induced vasodilation in vivo in xenografts, potentiating response to temozolomide. We now report that rucaparib inhibits the activity of the muscle contraction mediator myosin light chain kinase (MLCK) 10-fold more potently than its commercially available inhibitor ML-9. Moreover, rucaparib produces additive relaxation above the maximal degree achievable with ML-9, suggesting that MLCK inhibition is not solely responsible for dilation. Inhibition of nitric oxide synthesis using L-NMMA also failed to impact rucaparib’s activity. Rucaparib contains the nicotinamide pharmacophore, suggesting it may inhibit other NAD+-dependent processes. NAD⁺ exerts P2 purinergic receptor-dependent inhibition of smooth muscle contraction. Indiscriminate blockade of the P2 purinergic receptors with suramin abrogated rucaparib-induced vasodilation in rat arterial tissue without affecting ML-9-evoked dilation, although the specific receptor subtypes responsible have not been unequivocally identified. Furthermore, dorsal window chamber and real time tumor vessel perfusion analyses in PARP-1^-/- mice indicate a potential role for PARP in dilation of tumor-recruited vessels. Finally, rucaparib provoked relaxation in 70% of patient-derived tumor-associated vessels. These data provide tantalising evidence of the complexity of the mechanism underlying rucaparib-mediated vasodilation.     

Insights into the Dekkera bruxellensis Genomic Landscape: Comparative Genomics Reveals Variations in Ploidy and Nutrient Utilisation Potential amongst Wine Isolates

The yeast Dekkera bruxellensis is a major contaminant of industrial fermentations, such as those used for the production of biofuel and wine, where it outlasts and, under some conditions, outcompetes the major industrial yeast Saccharomyces cerevisiae. In order to investigate the level of inter-strain variation that is present within this economically important species, the genomes of four diverse D. bruxellensis isolates were compared. While each of the four strains was shown to contain a core diploid genome, which is clearly sufficient for survival, two of the four isolates have a third haploid complement of chromosomes. The sequences of these additional haploid genomes were both highly divergent from those comprising the diploid core and divergent between the two triploid strains. Similar to examples in the Saccharomyces spp. clade, where some allotriploids have arisen on the basis of enhanced ability to survive a range of environmental conditions, it is likely these strains are products of two independent hybridisation events that may have involved multiple species or distinct sub-species of Dekkera. Interestingly these triploid strains represent the vast majority (92%) of isolates from across the Australian wine industry, suggesting that the additional set of chromosomes may confer a selective advantage in winery environments that has resulted in these hybrid strains all-but replacing their diploid counterparts in Australian winery settings. In addition to the apparent inter-specific hybridisation events, chromosomal aberrations such as strain-specific insertions and deletions and loss-of-heterozygosity by gene conversion were also commonplace. While these events are likely to have affected many phenotypes across these strains, we have been able to link a specific deletion to the inability to utilise nitrate by some strains of D. bruxellensis, a phenotype that may have direct impacts in the ability for these strains to compete with S. cerevisiae.     

Factors influencing mutual gaze in captive female Japanese monkeys (<Emphasis Type="Italic">Macaca fuscata</Emphasis>)

Mutual gaze occurs when two animals simultaneously look at each other, and therefore signals reciprocal visual attention. We studied the occurrence of mutual gaze among adult female Japanese monkeys (Macaca fuscata) housed at the Central Park Zoo in New York City (USA). We found that the frequency of mutual gaze varied according to one aspect of social context (proximity), and that monkeys’ age-rank was negatively correlated with the frequency of mutual gaze. The behavioral contexts in which mutual gaze was observed did not include aggression, and social rank did not predict frequency of mutual gaze. Mutual gaze therefore varies according to some aspects of social context and is generally predicted by factors that influence other social behaviors (e.g., age).     

Caenorhabditis elegans HOPS and CCZ-1 mediate trafficking to lysosome-related organelles independently of RAB-7 and SAND-1

As early endosomes mature, the SAND-1/CCZ-1 complex acts as a guanine nucleotide exchange factor (GEF) for RAB-7 to promote the activity of its effector, HOPS, which facilitates late endosome–lysosome fusion and the consumption of AP-3–containing vesicles. We show that CCZ-1 and the HOPS complex are essential for the biogenesis of gut granules, cell type–specific, lysosome-related organelles (LROs) that coexist with conventional lysosomes in Caenorhabditis elegans intestinal cells. The HOPS subunit VPS-18 promotes the trafficking of gut granule proteins away from lysosomes and functions downstream of or in parallel to the AP-3 adaptor. CCZ-1 also acts independently of AP-3, and ccz-1 mutants mistraffic gut granule proteins. Our results indicate that SAND-1 does not participate in the formation of gut granules. In the absence of RAB-7 activity, gut granules are generated; however, their size and protein composition are subtly altered. These observations suggest that CCZ-1 acts in partnership with a protein other than SAND-1 as a GEF for an alternate Rab to promote gut granule biogenesis. Point mutations in GLO-1, a Rab32/38-related protein, predicted to increase spontaneous guanine nucleotide exchange, specifically suppress the loss of gut granules by ccz-1 and glo-3 mutants. GLO-3 is known to be required for gut granule formation and has homology to SAND-1/Mon1–related proteins, suggesting that CCZ-1 functions with GLO-3 upstream of the GLO-1 Rab, possibly as a GLO-1 GEF. These results support LRO formation occurring via processes similar to conventional lysosome biogenesis, albeit with key molecular differences.