Web Service Discovery in a Semantically Extended UDDI Registry: the Case of FUSION

Service-oriented computing is being adopted at an unprecedented rate, making the effectiveness of automated service discovery an increasingly important challenge. UDDI has emerged as a de facto industry standard and fundamental building block within SOA infrastructures. Nevertheless, conventional UDDI registries lack means to provide unambiguous, semantically rich representations of Web service capabilities, and the logic inference power required for facilitating automated service discovery. To overcome this important limitation, a number of approaches have been proposed towards augmenting Web service discovery with semantics. This paper discusses the benefits of semantically extending Web service descriptions and UDDI registries, and presents an overview of the approach put forward in project FUSION, towards semantically-enhanced publication and discovery of services based on SAWSDL

In vitro transport and satiety of a beta-lactoglobulin dipeptide and beta-casomorphin-7 and its metabolites

First published online 19 May 2014Understanding the digestive behaviour and biological activities of dairy proteins may help to develop model dairy products with targeted health outcomes including increased satiety and healthy weight maintenance. Caseins and whey proteins constitute over 95% of milk proteins with consumption of these proteins associated with increased satiety and a decreased prevalence of metabolic disorders. To investigate the in vitro digestive behaviour and satiety of dairy proteins at the intestinal epithelium, the in vitro transport and hydrolysis of 500-2000 μM β-casomorphin-7 (YPFPGPI or β-CM7) and a β-lactoglobulin (β-Lg) dipeptide (YL) was measured using Caco-2 cell monolayers grown on transwells as a model of the intestinal epithelium. Transport of YL was concentration dependent and ranged from 0.37-5.26 × 10(-6) cm s(-1), whereas transport of β-CM7 was only detected at 2000 μM and was significantly lower at 0.13 × 10(-6) cm s(-1). Rapid hydrolysis of β-CM7 in the apical chamber by the Caco-2 cells produced three peptide metabolites: YP, GPI and FPGPI. All of these metabolites were detected in the basolateral chamber after 30 min with both the YP and GPI peptides transporting at a higher rate than intact β-CM7. In vitro satiety was indicated by the secretion of cholecystokinin [26-33] (CCK-8) and glucagon-like peptide 1 (GLP-17-36NH2) in the STC-1 enteroendocrine cell model. CCK-8 secretion was highest in response to β-CM7 followed by the β-CM7 metabolite FPGPI. CCK-8 secretion however was not significantly stimulated by the tri- or dipeptides. Secretion of GLP-1 was not significantly stimulated by β-CM7 or YL. These in vitro results suggest that dairy peptide size enhances CCK-8 secretion, whilst limiting transport across Caco-2 monolayers.Simone Osborne, Wei Chen, Rama Addepalli, Michelle Colgrave, Tanoj Singh, Cuong Tran and Li Da

Alanine Scanning mutagenesis of the prototypic cyclotide reveals a cluster of residues essential for bioactivity

The cyclotides are stable plant-derived mini-proteins with a topologically circular peptide backbone and a knotted arrangement of three disulfide bonds that form a cyclic cystine knot structural framework. they display a wide range of pharmaceutically important bioactivities, but their natural function is in plant defense as insecticidal agents

Two proteins for the price of one: structural studies of the dual-destiny protein preproalbumin with sunflower trypsin inhibitor-1

Seed storage proteins are both an important source of nutrition for humans and essential for seedling establishment. Interestingly, unusual napin-type 2S seed storage albumin precursors in sunflowers contain a sequence that is released as a macrocyclic peptide during post-translational processing. The mechanism by which such peptides emerge from linear precursor proteins has received increased attention; however, the structural characterization of intact precursor proteins has been limited. Here, we report the 3D NMR structure of the Helianthus annuus PawS1 (preproalbumin with sunflower trypsin inhibitor-1) and provide new insights into the processing of this remarkable dual-destiny protein. In seeds, PawS1 is matured by asparaginyl endopeptidases (AEPs) into the cyclic peptide SFTI-1 (sunflower trypsin inhibitor-1) and a heterodimeric 2S albumin. The structure of PawS1 revealed that SFTI-1 and the albumin are independently folded into well-defined domains separated by a flexible linker. PawS1 was cleaved in vitro with recombinant sunflower HaAEP1 and in situ using a sunflower seed extract in a way that resembled the expected in vivo cleavages. Recombinant HaAEP1 cleaved PawS1 at multiple positions, and in situ, its flexible linker was removed, yielding fully mature heterodimeric albumin. Liberation and cyclization of SFTI-1, however, was inefficient, suggesting that specific seed conditions or components may be required for in vivo biosynthesis of SFTI-1. In summary, this study has revealed the 3D structure of a macrocyclic precursor protein and provided important mechanistic insights into the maturation of sunflower proalbumins into an albumin and a macrocyclic peptide

Qualità e grado di conservazione del paesaggio vegetale del litorale sabbioso del Veneto (Italia settentrionale).

Puberty is a complex physiological event by which animals mature into an adult capable of sexual reproduction. In order to enhance our understanding of the genes and regulatory pathways and networks involved in puberty, we characterized the transcriptome of five reproductive tissues (i.e. hypothalamus, pituitary gland, ovary, uterus, and endometrium) as well as tissues known to be relevant to growth and metabolism needed to achieve puberty (i.e., longissimus dorsi muscle, adipose, and liver). These tissues were collected from pre- and post-pubertal Brangus heifers (3/8 Brahman; Bos indicus x 5/8 Angus; Bos taurus) derived from a population of cattle used to identify quantitative trait loci associated with fertility traits (i.e., age of first observed corpus luteum (ACL), first service conception (FSC), and heifer pregnancy (HPG)). In order to exploit the power of complementary omics analyses, pre- and post-puberty co-expression gene networks were constructed by combining the results from genome-wide association studies (GWAS), RNA-Seq, and bovine transcription factors. Eight tissues among pre-pubertal and post-pubertal Brangus heifers revealed 1,515 differentially expressed and 943 tissue-specific genes within the 17,832 genes confirmed by RNA-Seq analysis. The hypothalamus experienced the most notable up-regulation of genes via puberty (i.e., 204 out of 275 genes). Combining the results of GWAS and RNA-Seq, we identified 25 loci containing a single nucleotide polymorphism (SNP) associated with ACL, FSC, and (or) HPG. Seventeen of these SNP were within a gene and 13 of the genes were expressed in uterus or endometrium. Multi-tissue omics analyses revealed 2,450 co-expressed genes relative to puberty. The pre-pubertal network had 372,861 connections whereas the post-pubertal network had 328,357 connections. A sub-network from this process revealed key transcriptional regulators (i.e., PITX2, FOXA1, DACH2, PROP1, SIX6, etc.). Results from these multi-tissue omics analyses improve understanding of the number of genes and their complex interactions for puberty in cattle

The Fusarium crown rot pathogen Fusarium pseudograminearum triggers a suite of transcriptional and metabolic changes in bread wheat (Triticum aestivum L.)

Background and Aims: Fusarium crown rot caused by the fungal pathogen Fusarium pseudograminearum is a disease of wheat and barley, bearing significant economic cost. Efforts to develop effective resistance to this disease have been hampered by the quantitative nature of resistance and a lack of understanding of the factors associated with resistance and susceptibility. Here, we aimed to dissect transcriptional responses triggered in wheat by F. pseudograminearum infection. Methods: We used an RNA-seq approach to analyse host responses during a compatible interaction and identified >2700 wheat genes differentially regulated after inoculation with F. pseudograminearum. The production of a few key metabolites and plant hormones in the host during the interaction was also analysed. Key Results: Analysis of gene ontology enrichment showed that a disproportionate number of genes involved in primary and secondary metabolism, signalling and transport were differentially expressed in infected seedlings. A number of genes encoding pathogen-responsive uridine-diphosphate glycosyltransferases (UGTs) potentially involved in detoxification of the Fusarium mycotoxin deoxynivalenol (DON) were differentially expressed. Using a F. pseudograminearum DON-non-producing mutant, DON was shown to play an important role in virulence during Fusarium crown rot. An over-representation of genes involved in the phenylalanine, tryptophan and tyrosine biosynthesis pathways was observed. This was confirmed through metabolite analyses that demonstrated tryptamine and serotonin levels are induced after F. pseudograminearum inoculation. Conclusions: Overall, the observed host response in bread wheat to F. pseudograminearum during early infection exhibited enrichment of processes related to pathogen perception, defence signalling, transport and metabolism and deployment of chemical and enzymatic defences. Additional functional analyses of candidate genes should reveal their roles in disease resistance or susceptibility. Better understanding of host responses contributing to resistance and/or susceptibility will aid the development of future disease improvement strategies against this important plant pathogen

Mead-halls of the Oiscingas: a new Kentish perspective on the Anglo-Saxon great hall complex phenomenon

Widely cited as a metaphor for the emergence of kingship in early medieval England, the great hall complex represents one of the most distinctive and evocative expressions of the Anglo-Saxon settlement record, yet interpretation of these sites remains underdeveloped and heavily weighted towards Yeavering. Inspired by the results of recent excavations at Lyminge, this paper undertakes a detailed comparative interrogation of three great hall complexes in Kent and exploits this new regional perspective to advance understanding of the agency and embodied meanings of these settlements as ‘theatres of power’. Explored through the thematic prisms of place, social memory and monumental hybridity, this examination leads to a new appreciation of the involvement of great hall sites in the genealogical strategies of 7th-century royal dynasties and a fresh perspective on how this remarkable yet short-lived monumental idiom was adapted to harness the symbolic capital of Romanitas

Interrogating and Predicting Tolerated Sequence Diversity in Protein Folds: Application to E. elaterium Trypsin Inhibitor-II Cystine-Knot Miniprotein

Cystine-knot miniproteins (knottins) are promising molecular scaffolds for protein engineering applications. Members of the knottin family have multiple loops capable of displaying conformationally constrained polypeptides for molecular recognition. While previous studies have illustrated the potential of engineering knottins with modified loop sequences, a thorough exploration into the tolerated loop lengths and sequence space of a knottin scaffold has not been performed. In this work, we used the Ecballium elaterium trypsin inhibitor II (EETI) as a model member of the knottin family and constructed libraries of EETI loop-substituted variants with diversity in both amino acid sequence and loop length. Using yeast surface display, we isolated properly folded EETI loop-substituted clones and applied sequence analysis tools to assess the tolerated diversity of both amino acid sequence and loop length. In addition, we used covariance analysis to study the relationships between individual positions in the substituted loops, based on the expectation that correlated amino acid substitutions will occur between interacting residue pairs. We then used the results of our sequence and covariance analyses to successfully predict loop sequences that facilitated proper folding of the knottin when substituted into EETI loop 3. The sequence trends we observed in properly folded EETI loop-substituted clones will be useful for guiding future protein engineering efforts with this knottin scaffold. Furthermore, our findings demonstrate that the combination of directed evolution with sequence and covariance analyses can be a powerful tool for rational protein engineering