bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fitting a geometric graph to a protein–protein interaction network
Authors: Higham Desmond J. , Rašajski Marija , Pržulj Nataša 
Published: March 2008

Abstract
Motivation: Finding a good network null model for protein–protein interaction (PPI) networks is a fundamental issue. Such a model would provide insights into the interplay between network structure and biological function as well as into evolution. Also, network (graph) models are used to guide biological experiments and discover new biological features. It has been proposed that geometric random graphs are a good model for PPI networks. In a geometric random graph, nodes correspond to uniformly randomly distributed points in a metric space and edges (links) exist between pairs of nodes for which the corresponding points in the metric space are close enough according to some distance norm. Computational experiments have revealed close matches between key topological properties of PPI networks and geometric random graph models. In this work, we push the comparison further by exploiting the fact that the geometric property can be tested for directly. To this end, we develop an algorithm that takes PPI interaction data and embeds proteins into a low-dimensional Euclidean space, under the premise that connectivity information corresponds to Euclidean proximity, as in geometric-random graphs. We judge the sensitivity and specificity of the fit by computing the area under the Receiver Operator Characteristic (ROC) curve. The network embedding algorithm is based on multi-dimensional scaling, with the square root of the path length in a network playing the role of the Euclidean distance in the Euclidean space. The algorithm exploits sparsity for computational efficiency, and requires only a few sparse matrix multiplications, giving a complexity of O(N2) where N is the number of proteins.
Results: The algorithm has been verified in the sense that it successfully rediscovers the geometric structure in artificially constructed geometric networks, even when noise is added by re-wiring some links. Applying the algorithm to 19 publicly available PPI networks of various organisms indicated that: (a) geometric effects are present and (b) two-dimensional Euclidean space is generally as effective as higher dimensional Euclidean space for explaining the connectivity. Testing on a high-confidence yeast data set produced a very strong indication of geometric structure (area under the ROC curve of 0.89), with this network being essentially indistinguishable from a noisy geometric network. Overall, the results add support to the hypothesis that PPI networks have a geometric structure.
Availability: MATLAB code implementing the algorithm is available upon request.
Contact: natasha@ics.uci.edu
Biological sequence classification utilizing positive and unlabeled data
Authors: Xiao Yuanyuan , Segal Mark R. 
Published: March 2008

Abstract
Motivation: In the genomics setting, an increasingly common data configuration consists of a small set of sequences possessing a targeted property (positive instances) amongst a large set of sequences for which class membership is unknown (unlabeled instances). Traditional two-class classification methods do not effectively handle such data.
Results: Here, we develop a novel method, likely positive-iterative classification (LP-IC) for this problem, and contrast its performance with the few existing methods, most of which were devised and utilized in the text classification context. LP-IC employs an iterative classification scheme and introduces a class dispersion measure, adopted from unsupervised clustering approaches, to monitor the model selection process. Using two case studies—prediction of HLA binding, and alternative splicing conservation between human and mouse—we show that LP-IC provides superior performance to existing methodologies in terms of: (i) combined accuracy and precision in positive identification from the unlabeled set; and (ii) predictive performance of the resultant classifiers on independent test data.
Contact: mark@biostat.ucsf.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Impact of climate change on long-term zooplankton biomass in the upwelling region of the Gulf of Guinea
Authors: Wiafe George , Yaqub Hawa B. , Mensah Martin A. , Frid Christopher L. J. 
Published: March 2008

Abstract
Wiafe, G., Yaqub, H. B., Mensah, M. A., and Frid, C. L. J. 2008. Impact of climate change on long-term zooplankton biomass in the upwelling region of the Gulf of Guinea. – ICES Journal of Marine Science, 65: 318–324. We investigated long-term changes in coastal zooplankton in the upwelling region in the Gulf of Guinea, 1969–1992, in relation to climatic and biotic factors. We considered the role of hydrographic and climatic factors, i.e. sea surface temperature (SST), salinity, sea level pressure, windfield, and Southern Oscillation Index (SOI), in the long-term variation of zooplankton in a multiple regression analysis, along with the abundance of Sardinella. Annual variation in zooplankton biomass was cyclical, with the annual peak occurring during the major upwelling season, July–September. Over the 24-year period, there was a downward trend in zooplankton biomass (equivalent to 6.33 ml per 1000 m3 per year). The decomposed trend in SST during the major upwelling revealed gradual warming of surface waters. This trend was believed to be the main influence on the abundance of the large copepod Calanoides carinatus (sensitive to temperatures above 23°C), which appears in the coastal waters only during the major upwelling season. The warming trend associated with global climate change could affect zooplankton community structure, especially during the major upwelling season. Global warming coupled with “top–down” (predation) control by Sardinella might be responsible for the long-term decline in zooplankton biomass in the upwelling region of the Gulf of Guinea.
Cell Wall Modifications in Arabidopsis Plants with Altered α-l-Arabinofuranosidase Activity
Authors: Chávez Montes Ricardo A. , Ranocha Philippe , Martinez Yves , Minic Zoran , Jouanin Lise , Marquis Mélanie , Saulnier Luc , Fulton Lynette M. , Cobbett Christopher S. , Bitton Frédérique , Renou Jean-Pierre , Jauneau Alain , Goffner Deborah 
Published: March 2008

Abstract
Although cell wall remodeling is an essential feature of plant growth and development, the underlying molecular mechanisms are poorly understood. This work describes the characterization of Arabidopsis (Arabidopsis thaliana) plants with altered expression of ARAF1, a bifunctional α-l-arabinofuranosidase/β-d-xylosidase (At3g10740) belonging to family 51 glycosyl-hydrolases. ARAF1 was localized in several cell types in the vascular system of roots and stems, including xylem vessels and parenchyma cells surrounding the vessels, the cambium, and the phloem. araf1 T-DNA insertional mutants showed no visible phenotype, whereas transgenic plants that overexpressed ARAF1 exhibited a delay in inflorescence emergence and altered stem architecture. Although global monosaccharide analysis indicated only slight differences in cell wall composition in both mutant and overexpressing lines, immunolocalization experiments using anti-arabinan (LM6) and anti-xylan (LM10) antibodies indicated cell type-specific alterations in cell wall structure. In araf1 mutants, an increase in LM6 signal intensity was observed in the phloem, cambium, and xylem parenchyma in stems and roots, largely coinciding with ARAF1 expression sites. The ectopic overexpression of ARAF1 resulted in an increase in LM10 labeling in the secondary walls of interfascicular fibers and xylem vessels. The combined ARAF1 gene expression and immunolocalization studies suggest that arabinan-containing pectins are potential in vivo substrates of ARAF1 in Arabidopsis.
Sucrose Synthase Is Associated with the Cell Wall of Tobacco Pollen Tubes
Authors: Persia Diana , Cai Giampiero , Del Casino Cecilia , Faleri Claudia , Willemse Michiel T.M. , Cresti Mauro 
Published: March 2008

AbstractSucrose synthase (Sus; EC 2.4.1.13) is a key enzyme of sucrose metabolism in plant cells, providing carbon for respiration and for the synthesis of cell wall polymers and starch. Since Sus is important for plant cell growth, insights into its structure, localization, and features are useful for defining the relationships between nutrients, growth, and cell morphogenesis. We used the pollen tube of tobacco (Nicotiana tabacum) as a cell model to characterize the main features of Sus with regard to cell growth and cell wall synthesis. Apart from its role during sexual reproduction, the pollen tube is a typical tip-growing cell, and the proper construction of its cell wall is essential for correct shaping and direction of growth. The outer cell wall layer of pollen tubes consists of pectins, but the inner layer is composed of cellulose and callose; both polymers require metabolic precursors in the form of UDP-glucose, which is synthesized by Sus. We identified an 88-kD polypeptide in the soluble, plasma membrane and Golgi fraction of pollen tubes. The protein was also found in association with the cell wall. After purification, the protein showed an enzyme activity similar to that of maize (Zea mays) Sus. Distribution of Sus was affected by brefeldin A and depended on the nutrition status of the pollen tube, because an absence of metabolic sugars in the growth medium caused Sus to distribute differently during tube elongation. Analysis by bidimensional electrophoresis indicated that Sus exists as two isoforms, one of which is phosphorylated and more abundant in the cytoplasm and cell wall and the other of which is not phosphorylated and is specific to the plasma membrane. Results indicate that the protein has a role in the construction of the extracellular matrix and thus in the morphogenesis of pollen tubes.
Comparison of the Dynamics and Functional Redundancy of the Arabidopsis Dynamin-Related Isoforms DRP1A and DRP1C during Plant Development
Authors: Konopka Catherine A. , Bednarek Sebastian Y. 
Published: March 2008

Abstract
Members of the Arabidopsis (Arabidopsis thaliana) DYNAMIN-RELATED PROTEIN1 (DRP1) family are required for cytokinesis and cell expansion. Two isoforms, DRP1A and DRP1C, are required for plasma membrane maintenance during stigmatic papillae expansion and pollen development, respectively. It is unknown whether the DRP1s function interchangeably or if they have distinct roles during cell division and expansion. DRP1C was previously shown to form dynamic foci in the cell cortex, which colocalize with part of the clathrin endocytic machinery in plants. DRP1A localizes to the plasma membrane, but its cortical organization and dynamics have not been determined. Using dual color labeling with live cell imaging techniques, we showed that DRP1A also forms discreet dynamic foci in the epidermal cell cortex. Although the foci overlap with those formed by DRP1C and clathrin light chain, there are clear differences in behavior and response to pharmacological inhibitors between DRP1A and DRP1C foci. Possible functional or regulatory differences between DRP1A and DRP1C were supported by the failure of DRP1C to functionally compensate for the absence of DRP1A. Our studies indicated that the DRP1 isoforms function or are regulated differently during cell expansion.
Characterization of an Amino Acid Permease from the Endomycorrhizal Fungus Glomus mosseae
Authors: Cappellazzo Gilda , Lanfranco Luisa , Fitz Michael , Wipf Daniel , Bonfante Paola 
Published: March 2008

Abstract
Arbuscular mycorrhizal (AM) fungi are capable of exploiting organic nitrogen sources, but the molecular mechanisms that control such an uptake are still unknown. Polymerase chain reaction-based approaches, bioinformatic tools, and a heterologous expression system have been used to characterize a sequence coding for an amino acid permease (GmosAAP1) from the AM fungus Glomus mosseae. The GmosAAP1 shows primary and secondary structures that are similar to those of other fungal amino acid permeases. Functional complementation and uptake experiments in a yeast mutant that was defective in the multiple amino acid uptake system demonstrated that GmosAAP1 is able to transport proline through a proton-coupled, pH- and energy-dependent process. A competitive test showed that GmosAAP1 binds nonpolar and hydrophobic amino acids, thus indicating a relatively specific substrate spectrum. GmosAAP1 mRNAs were detected in the extraradical fungal structures. Transcript abundance was increased upon exposure to organic nitrogen, in particular when supplied at 2 mm concentrations. These findings suggest that GmosAAP1 plays a role in the first steps of amino acid acquisition, allowing direct amino acid uptake from the soil and extending the molecular tools by which AM fungi exploit soil resources.
TheArabidopsisP4-ATPase ALA3 Localizes to the Golgi and Requires a β-Subunit to Function in Lipid Translocation and Secretory Vesicle Formation
Authors: Poulsen Lisbeth Rosager , López-Marqués Rosa Laura , McDowell Stephen C. , Okkeri Juha , Licht Dirk , Schulz Alexander , Pomorski Thomas , Harper Jeffrey F. , Palmgren Michael Gjedde 
Published: March 2008

AbstractVesicle budding in eukaryotes depends on the activity of lipid translocases (P4-ATPases) that have been implicated in generating lipid asymmetry between the two leaflets of the membrane and in inducing membrane curvature. We show that Aminophospholipid ATPase3 (ALA3), a member of the P4-ATPase subfamily in Arabidopsis thaliana, localizes to the Golgi apparatus and that mutations of ALA3 result in impaired growth of roots and shoots. The growth defect is accompanied by failure of the root cap to release border cells involved in the secretion of molecules required for efficient root interaction with the environment, and ala3 mutants are devoid of the characteristic trans-Golgi proliferation of slime vesicles containing polysaccharides and enzymes for secretion. In yeast complementation experiments, ALA3 function requires interaction with members of a novel family of plant membrane-bound proteins, ALIS1 to ALIS5 (for ALA-Interacting Subunit), and in this host ALA3 and ALIS1 show strong affinity for each other. In planta, ALIS1, like ALA3, localizes to Golgi-like structures and is expressed in root peripheral columella cells. We propose that the ALIS1 protein is a β-subunit of ALA3 and that this protein complex forms an important part of the Golgi machinery required for secretory processes during plant development.
EMB2473/MIRO1, anArabidopsisMiro GTPase, Is Required for Embryogenesis and Influences Mitochondrial Morphology in Pollen
Authors: Yamaoka Shohei , Leaver Christopher J. 
Published: March 2008

AbstractThe regulation of mitochondrial biogenesis, subcellular distribution, morphology, and metabolism are essential for all aspects of plant growth and development. However, the molecular mechanisms involved are still unclear. Here, we describe an analysis of the three Arabidopsis thaliana orthologs of the evolutionarily conserved Miro GTPases. Two of the genes, MIRO1 and MIRO2, are transcribed ubiquitously throughout the plant tissues, and their gene products localize to mitochondria via their C-terminal transmembrane domains. While insertional mutations in the MIRO2 gene do not have any visible impact on plant development, an insertional mutation in the MIRO1 gene is lethal during embryogenesis at the zygote to four-terminal-cell embryo stage. It also substantially impairs pollen germination and tube growth. Laser confocal and transmission electron microscopy revealed that the miro1 mutant pollen exhibits abnormally enlarged or tube-like mitochondrial morphology, leading to the disruption of continuous streaming of mitochondria in the growing pollen tube. Our findings suggest that mitochondrial morphology is influenced by MIRO1 and plays a vital role during embryogenesis and pollen tube growth.
The Coiled-Coil and Nucleotide Binding Domains of the Potato Rx Disease Resistance Protein Function in Pathogen Recognition and Signaling
Authors: Rairdan Gregory J. , Collier Sarah M. , Sacco Melanie A. , Baldwin Thomas T. , Boettrich Teresa , Moffett Peter 
Published: March 2008

AbstractPlant genomes encode large numbers of nucleotide binding and leucine-rich repeat (NB-LRR) proteins, some of which mediate the recognition of pathogen-encoded proteins. Following recognition, the initiation of a resistance response is thought to be mediated by the domains present at the N termini of NB-LRR proteins, either a Toll and Interleukin-1 Receptor or a coiled-coil (CC) domain. In order to understand the role of the CC domain in NB-LRR function, we have undertaken a systematic structure–function analysis of the CC domain of the potato (Solanum tuberosum) CC-NB-LRR protein Rx, which confers resistance to Potato virus X. We show that the highly conserved EDVID motif of the CC domain mediates an intramolecular interaction that is dependent on several domains within the rest of the Rx protein, including the NB and LRR domains. Other conserved and nonconserved regions of the CC domain mediate the interaction with the Ran GTPase–activating protein, RanGAP2, a protein required for Rx function. Furthermore, we show that the Rx NB domain is sufficient for inducing cell death typical of hypersensitive plant resistance responses. We describe a model of CC-NB-LRR function wherein the LRR and CC domains coregulate the signaling activity of the NB domain in a recognition-specific manner.
TUMOUR AND PLASMA ACTH CONCENTRATIONS IN PATIENTS WITH AND WITHOUT THE ECTOPIC ACTH SYNDROME
Authors: RATCLIFFE J. G. , KNIGHT R. A. , BESSER G. M. , LANDON J. , STANSFELD A. G. 
Published: March 2008

SUMMARYBioactive and immunoreactive corticotrophin (ACTH) concentrations in seventeen tumours from patients with the ectopic ACTH syndrome were compared with those in fourteen ‘control’tumours from patients without the syndrome. Each of the ‘control’tumours showed ACTH activity greater than in non‐tumorous tissue and the range of concentrations overlapped with the ‘ectopic ACTH’group. The presence of significant ACTH activity in every tumour studied suggests that hormone production may be a common feature of neoplasia in the absence of clinically obvious sequelae of excess circulating hormone. Tumours associated with the ectopic ACTH syndrome showed a wide range of ACTH activities: bronchial carcinoid tumours generally contained higher levels than oat cell carcinomas of the bronchus and more C‐ than N‐terminal ACTH activity. In twenty‐four patients with the clinical syndrome the plasma ACTH levels were not clearly related to tumour type; the levels ranged between 100 and 10,000 pg/ml, showed an abnormal nyctohemeral rhythm, and fell following successful removal of the tumour.
SUBCUTANEOUS GLUCAGON AS A TEST OF THE ABILITY OF THE PITUITARY TO SECRETE GH AND ACTH
Authors: SPATHIS G. S. , BLOOM S. R. , JEFFCOATE W. J. , MILLAR J. G. B. , KURTZ A. , PYASENA M. R. D. , SMITH JEANNE A. , NABARRO J. D. N. 
Published: March 2008

SUMMARYThe response to the subcutaneous injection of glucagon (1 mg) has been studied as a test of the ability of the pituitary to secrete ACTH and growth hormone (GH). Tests have been performed on fifteen normal subjects or patients with unrelated conditions, nine patients with pituitary tumours and seventeen with acromegaly. It is suggested that a normal response is a peak level of 5 ng/ml or more of GH (standard NIH GH 1216C) and either a rise of plasma cortisol measured by competitive protein binding of at least 4 μg/100 ml or a peak level of 7 μg/100 ml. In seventeen patients the responses were compared with those obtained in the insulin hypoglycaemia test and there was good agreement. Measurement of plasma ACTH showed that the response is at pituitary and not adrenal cortical level. Peak responses of ACTH and GH were obtrained at 150 min and of cortisol at 180 min. Plasma glucagon concentrations were falling steadily by this time although still above the control level. The mechanism of action of glucagon is not clear but does not appear to be related to fall of blood sugar. The subcutaneous injection of glucagon is not without side effects; about half the patients were nauseated and nine vomited. Nevertheless we believe that a subcutaneous glucagon test is of value for testing the pituitary reserve of ACTH and GH in situations where insulin hypoglycaemia cannot be used.
THE EFFECT OF THE INTESTINAL POLYPEPTIDES, IRP AND GIP, ON INSULIN|RELEASE AND GLUCOSE TOLERANCE IN THE BABOON
Authors: TURNER D. S. , ETHERIDGE LAURAINE , JONES JULIE , MARKS V. , MELDRUM B. , BLOOM S. R. , BROWN J. C. 
Published: March 2008

The recently isolated intestinal polypeptides, intestinal insulin releasing polypeptide (IRP) and gastric inhibitory polypeptide (GIP), have been shown to potentiate glucose stimulated insulin release in the baboon. The effect was similar to that seen in the rat and demonstrates that both peptides affect insulin release in a broad range of species. No effect on glucagon release was observed. The possibility that either IRP or GIP, or both, is involved in the alimentary augmentation of insulin release by oral glucose deserves consideration.It is now well recognized that intestinal hormones are concerned in the regulation of glucose homeostasis (McIntyre et al., 1964; Marks & Samols, 1970), but their absolute identity and relative importance is uncertain.Two recently isolated polypeptides, intestinal insulin releasing polypeptide (IRP) (Turner, 1972; Turner et al., 1973) and gastric inhibitory polypeptide (GIP) (Brown et al., 1969), have been shown to produce dramatic effects on the insulinaemic response to intravenous glucose in the rat (Turner et al., 1973; Dupré, 1973). In order to determine whether these effects are limited to the rat, or a general phenomenon, the ability of the two peptides to augment the insulin response to intravenous glucose was examined in the baboon, Papio papio. In view of the known suppressive effect of oral glucose on glucagon release, plasma glucagon levels were also measured.
THE EFFECTS OF LARGE DOSES OF THE ANABOLIC STEROID, METHANDROSTENOLONE, ON AN ATHLETE
Authors: KILSHAW B. H. , HARKNESS R. A. , HOBSON B. M. , SMITH A. W. M. 
Published: March 2008

SUMMARYDoses of the anabolic steroid, methandrostenolone, nearly ten times greater than those used therapeutically, have resulted in a marked depression of levels of testosterone in urine and blood, and in some depression of gonadotrophin excretion by a male athlete.The administration of the durg has been checked and its metabolism studied from the pattern of urinary metabolites.