Predicting functional gene links from phylogenetic-statistical analyses of whole genomes

An important element of the developing field of proteomics is to understand protein-protein interactions and other functional links amongst genes. Across-species correlation methods for detecting functional links work on the premise that functionally linked proteins will tend to show a common pattern of presence and absence across a range of genomes. We describe a maximum likelihood statistical model for predicting functional gene linkages. The method detects independent instances of the correlated gain or loss of pairs of proteins on phylogenetic trees, reducing the high rates of false positives observed in conventional across-species methods that do not explicitly incorporate a phylogeny. We show, in a dataset of 10,551 protein pairs, that the phylogenetic method improves by up to 35% on across-species analyses at identifying known functionally linked proteins. The method shows that protein pairs with at least two to three correlated events of gain or loss are almost certainly functionally linked. Contingent evolution, in which one gene's presence or absence depends upon the presence of another, can also be detected phylogenetically, and may identify genes whose functional significance depends upon its interaction with other genes. Incorporating phylogenetic information improves the prediction of functional linkages. The improvement derives from having a lower rate of false positives and from detecting trends that across-species analyses miss. Phylogenetic methods can easily be incorporated into the screening of large-scale bioinformatics datasets to identify sets of protein links and to characterise gene networks.

High-throughput proteomics using matrix-assisted laser desorption/ ionization mass spectrometry

It has become evident that the mystery of life will not be deciphered just by decoding its blueprint, the genetic code. In the life and biomedical sciences, research efforts are now shifting from pure gene analysis to the analysis of all biomolecules involved in the machinery of life. One area of these postgenomic research fields is proteomics. Although proteomics, which basically encompasses the analysis of proteins, is not a new concept, it is far from being a research field that can rely on routine and large-scale analyses. At the time the term proteomics was coined, a gold-rush mentality was created, promising vast and quick riches (i.e., solutions to the immensely complex questions of life and disease). Predictably, the reality has been quite different. The complexity of proteomes and the wide variations in the abundances and chemical properties of their constituents has rendered the use of systematic analytical approaches only partially successful, and biologically meaningful results have been slow to arrive. However, to learn more about how cells and, hence, life works, it is essential to understand the proteins and their complex interactions in their native environment. This is why proteomics will be an important part of the biomedical sciences for the foreseeable future. Therefore, any advances in providing the tools that make protein analysis a more routine and large-scale business, ideally using automated and rapid analytical procedures, are highly sought after. This review will provide some basics, thoughts and ideas on the exploitation of matrix-assisted laser desorption/ ionization in biological mass spectrometry - one of the most commonly used analytical tools in proteomics - for high-throughput analyses.

Post-haemorrhagic anaemia in sea bass, Dicentrarchus labrax (L.), caused by blood feeding of Ceratothoa oestroides (Isopoda: Cymothoidae)

The effects of the fish parasitic isopod, Ceratothoa oestroides (Risso), on haematological parameters of its cage-cultured sea bass host, Dicentrarchus labrax (L.), were studied. Analyses of blood parameters (cell counts, haemoglobin content and haematocrit) were carried out on parasitized and unparasitized sea bass from a fish farm in Turkey. Parasitized fish had significantly lowered erythrocyte counts, haematocrit and haemoglobin values and significantly increased leucocyte counts. Blood feeding by C. oestroides thus produces a post-haemorrhagic anaemia and the fish appear to mount an immune response to the presence of parasites.

Inter-simple sequence repeat and aggressiveness analyses revealed high genetic diversity, recombination and long-range dispersal in Fusarium culmorum

Inter-simple sequence repeat (ISSR) analysis and aggressiveness assays were used to investigate genetic variability within a global collection of Fusarium culmorum isolates. A set of four ISSR primers were tested, of which three primers amplified a total of 37 bands out of which 30 (81%) were polymorphic. The intraspecific diversity was high, ranging from four to 28 different ISSR genotypes for F. culmorum depending on the primer. The combined analysis of ISSR data revealed 59 different genotypes clustered into seven distinct clades amongst 75 isolates of F. culmorum examined. All the isolates were assayed to test their aggressiveness on a winter wheat cv. 'Armada'. A significant quantitative variation for aggressiveness was found among the isolates. The ISSR and aggressiveness variation existed on a macro- as well as micro-geographical scale. The data suggested a long-range dispersal of F. culmorum and indicated that this fungus may have been introduced into Canada from Europe. In addition to the high level of intraspecific diversity observed in F. culmorum, the index of multilocus association calculated using ISSR data indicated that reproduction in F. culmorum cannot be exclusively clonal and recombination is likely to occur.

Inhibition of vascular smooth muscle cell proliferation by non-steroidal anti-inflammatory drugs

Abnormal vascular smooth muscle cell (VSMC) proliferation is known to play an important role in the pathogenesis of atherosclerosis, restenosis and instent stenosis. Recent studies suggest that salicylates, in addition to inhibiting cyclooxygenase activity, exert an antiproliferative effect on VSMC growth both in vitro and in vivo. However, whether all non-steroidal anti-inflammatory drugs (NSAID) exert similar antiproliferative effects on VSMCs, and do so via a common mechanism of action, remains unknown. In the present study, we demonstrated that the NSAIDs, aspirin, ibuprofen and sulindac induced a dose-dependent inhibition of proliferation in rat A10 VSMCs (IC50 = 1666 mumol/L, 937 mumol/L and 520 mumol/L, respectively). These drugs did not show significant cytotoxic effects as determined by LDH release assay, even at the highest concentrations tested (aspirin, 5000 mumol/L; ibuprofen, 2500 mumol/L; and sulindac, 1000 mumol/L). Flow cytometric analyses showed that a 48 h exposure of A10 VSMCs to ibuprofen (1000 mumol/L) and sulindac (750 mumol/L) led to a significant G1 arrest (from 68.7 +/- 2.0% of cells in G1 to 76.6 +/- 2.2% and 75.8 +/- 2.2%, respectively, p < 0.05). In contrast, aspirin (2500 mumol/L) failed to induce a significant G1 arrest (68.1 +/- 5.2%). Clearer evidence of a G1 block was obtained by treatment of cells with the mitotic inhibitor, nocodazole (40 ng/ml), for the final 24 h of the experiment. Under these conditions, aspirin still failed to induce a G1 arrest (from 25.9 +/- 10.9% of cells in G1 to 19.6 +/- 2.3%) whereas ibuprofen and sulindac led to a significant accumulation of cells in G1(51.8% +/- 17.2% and 54.1% +/- 10.6%, respectively, p < 0.05). These results indicate that ibuprofen and sulindac inhibit VSMC proliferation by arresting the cell cycle in the G1 phase whereas the effect of aspirin appears to be independent of any special phase of the cell cycle. Irrespective of mechanism, our results suggest that NSAIDs might be of benefit to the treatment of vascular proliferative disorders.

Syntheses, structural analyses, and magneto-structural correlations of three polymeric Fe(II) complexes with azide ligand

Three new metal-organic polymeric complexes, [Fe(N-3)(2)(bPP)(2)] (1), [Fe(N-3)(2)(bpe)] (2), and [Fe(N-3)(2)(phen)] (3) [bpp = (1,3-bis(4-pyridyl)-propane), bpe = (1,2-bis(4-pyridyl)-ethane), phen = 1,10-phenanthroline], have been synthesized and characterized by single-crystal X-ray diffraction studies and low-temperature magnetic measurements in the range 300-2 K. Complexes 1 and 2 crystallize in the monoclinic system, space group C2/c, with the following cell parameters: a = 19.355(4) Angstrom, b = 7.076(2) Angstrom, c = 22.549(4) Angstrom, beta = 119.50(3)degrees, Z = 4, and a = 10.007(14) Angstrom, b = 13.789(18) Angstrom, c = 10.377(14) Angstrom, beta = 103.50(1)degrees, Z = 4, respectively. Complex 3 crystallizes in the triclinic system, space group P (1) over bar, with a = 7.155(12) Angstrom, b = 10.066(14) Angstrom, c = 10.508(14) Angstrom, alpha = 109.57(1)degrees, beta = 104.57(1)degrees, gamma = 105.10(1)degrees, and Z = 2. All coordination polymers exhibit octahedral Fe(II) nodes. The structural determination of 1 reveals a parallel interpenetrated structure of 2D layers of (4,4) topology, formed by Fe(II) nodes linked through bpp ligands, while mono-coordinated azide anions are pendant from the corrugated sheet. Complex 2 has a 2D arrangement constructed through 1D double end-to-end azide bridged iron(11) chains interconnected through bpe ligands. Complex 3 shows a polymeric arrangement where the metal ions are interlinked through pairs of end-on and end-to-end azide ligands exhibiting a zigzag arrangement of metals (Fe-Fe-Fe angle of 111.18degrees) and an intermetallic separation of 3.347 Angstrom (through the EO azide) and of 5.229 Angstrom (EE azide). Variable-temperature magnetic susceptibility data suggest that there is no magnetic interaction between the metal centers in 1, whereas in 2 there is an antiferromagnetic interaction through the end-to-end azide bridge. Complex 3 shows ferro- as well as anti-ferromagnetic interactions between the metal centers generated through the alternating end-on and end-to-end azide bridges. Complex I has been modeled using the D parameter (considering distorted octahedral Fe(II) geometry and with any possible J value equal to zero) and complex 2 has been modeled as a one-dimensional system with classical and/or quantum spin where we have used two possible full diagonalization processes: without and with the D parameter, considering the important distortions of the Fe(II) ions. For complex 3, the alternating coupling model impedes a mathematical solution for the modeling as classical spins. With quantum spin, the modeling has been made as in 2.

Liquid matrices for analyses by UV-MALDI mass spectrometry

Data are presented for a pH-adjustable liquid UV-matrix-assisted laser desorption ionization (MALDI) matrix for mass spectrometry analysis. The liquid matrix system possesses high analytical sensitivity within the same order of magnitude as that achievable by the commonly used solid UV-MALDI matrices such as 2,5-dihydroxybenzoic acid but with improved spot homogeneity and reproducibility. The pH of the matrix has been adjusted by the addition of up to 0.35% trifluoroacetic acid and up to 200 mM ammonium bicarbonate, achieving an on-target pH range of 3.5-8.6. Alteration of the pH does not seem to affect the overall sample signal intensity or signal-to-noise ratio achievable, nor does it affect the individual peptide ion signals from a mixture of peptides with varying isoelectric points (p1). In addition, the pH adjustment has allowed for the performance of a tryptic digest within the diluted pH-optimized liquid matrix.

Landscape state machines: Tools for evolutionary algorithm performance analyses and landscape/algorithm mapping

Many evolutionary algorithm applications involve either fitness functions with high time complexity or large dimensionality (hence very many fitness evaluations will typically be needed) or both. In such circumstances, there is a dire need to tune various features of the algorithm well so that performance and time savings are optimized. However, these are precisely the circumstances in which prior tuning is very costly in time and resources. There is hence a need for methods which enable fast prior tuning in such cases. We describe a candidate technique for this purpose, in which we model a landscape as a finite state machine, inferred from preliminary sampling runs. In prior algorithm-tuning trials, we can replace the 'real' landscape with the model, enabling extremely fast tuning, saving far more time than was required to infer the model. Preliminary results indicate much promise, though much work needs to be done to establish various aspects of the conditions under which it can be most beneficially used. A main limitation of the method as described here is a restriction to mutation-only algorithms, but there are various ways to address this and other limitations.

A comparison of extra-tropical cyclones in recent re-analyses; ERA-Interim, NASA MERRA, NCEP CFSR and JRA-25

Extra-tropical cyclones are identified and compared using data from four recent re-analyses for the winter periods in both hemispheres. Results show the largest differences occur between the older lower resolution JRA25 re-analysis when compared with the newer high resolution re-analyses, in particular in the Southern Hemisphere (SH). Spatial differences between the newest re-analyses are small in both hemispheres and generally not significant except some common regions associated with cyclogenesis close to orography. Intensities are generally related to spatial resolution except NASA-MERRA which has larger intensities for several different measures. Matching storms between re-analyses shows the number matched between ERA-Interim and the other re-analyses are similar in the Northern Hemisphere (NH). In the SH the number matched between JRA25 and ERA-Interim is lower than in the NH, but for NASA-MERRA and NCEP-CFSR the number matched is similar to the NH. The mean separation of the identically same cyclones is typically less than 20 geodesic in both hemispheres for the latest re-analyses, whereas JRA25 compared with the other re-analyses has a broader distribution in the SH indicating greater uncertainty. The instantaneous intensity differences for matched storms shows narrow distributions for pressure while for winds and vorticity the distributions are much broader indicating larger uncertainty typical of smaller scale fields. Composite cyclone diagnostics show that cyclones are very similar between the re-analyses, with differences being related to the intensities, consistent with the intensity results. Overall, results show NH cyclones correspond well between re-analyses, with a significant improvement in the SH for the latest re-analyses, indicating a convergence between re-analyses for cyclone properties.

Tenant mix variety in regional shopping centres: some UK empirical analyses

The variety and quality of the tenant mix within a shopping centre is a key concern in shopping centre management. Tenant mix determines the extent of externalities between outlets in the centre, helps establish the image of the centre and, as a result, determines the attractiveness of the centre for consumers. This then translates into sales and rents. However, the management of tenant mix has largely been based on perceived “optimum” arrangements and industry rules of thumb. This paper attempts to model the impact of tenant mix on the rent paid by retailers in larger UK shopping centres and, hence, the returns made by shopping centre landlords. It extends work on shopping centre rent determination (see Working Paper 10/03) utilising a database of 148 regional shopping centres in the UK, with detailed data for over 1900 tenants. Econometric models test the relationship between rental levels and the levels of retail concentration and diversity, while controlling for a range of continuous and qualitative characteristics of each tenant, each retail product, and each shopping centre. Factor analysis is then used to extract the core retail and service categories from the tenant lists of the 148 shopping centres. The factor scores from these core retailer factors are then tested against rent payable. The results from the empirical analysis allow us to generate some clear analytical and empirical implications for optimal retail management.

Citation and peer review of data: moving towards formal data publication

This paper discusses many of the issues associated with formally publishing data in academia, focusing primarily on the structures that need to be put in place for peer review and formal citation of datasets. Data publication is becoming increasingly important to the scientific community, as it will provide a mechanism for those who create data to receive academic credit for their work and will allow the conclusions arising from an analysis to be more readily verifiable, thus promoting transparency in the scientific process. Peer review of data will also provide a mechanism for ensuring the quality of datasets, and we provide suggestions on the types of activities one expects to see in the peer review of data. A simple taxonomy of data publication methodologies is presented and evaluated, and the paper concludes with a discussion of dataset granularity, transience and semantics, along with a recommended human-readable citation syntax.

Sensory and instrumental analyses of volatiles generated during the extrusion cooking of oat flours

Three batches of oats were extruded under four combinations of process temperature (150 or 180 °C) and process moisture (14.5 and 18%). Two of the extrudates were evaluated by a sensory panel, and three were analyzed by GC-MS. Maillard reaction products, such as pyrazines, pyrroles, furans, and sulfur-containing compounds, were found in the most severely processed extrudates (high-temperature, low-moisture). These extrudates were also described by the assessors as having toasted cereal attributes. Lipid degradation products, such as alkanals, 2-alkenals, and 2,4-alkadienals, were found at much higher levels in the extrudates of the oat flour that had been debranned. It contained lower protein and fiber levels than the others and showed increased lipase activity. Extrudates from these samples also had significantly lower levels of Maillard reaction products that correlated, in the sensory analysis, with terms such as stale oil and oatmeal. Linoleic acid was added to a fourth oat flour to simulate the result of increased lipase activity, and GC-MS analysis showed both an increase in lipid degradation products and a decrease in Maillard reaction products.