Threshold consensus methods for molecular sequences.

We introduce a parameterized threshold consensus method (th chi) for molecular sequences which is based on a majority-rule voting principle. In contrast to other frequency-based methods, the th chi method uses a single criterion to return ambiguity codes of different lengths. We derive basic features of the method and establish that it returns at most two ambiguity codes at any position of the consensus sequence. We bound from below the size of the frequency gap that exists when the th chi method returns an ambiguity code. Using such properties, we compare the th chi method to other consensus methods for molecular sequences which are defined in terms of threshold or gap criteria.     

Spectroscopic characterisation of n-octanohydroxamic acid and potassium hydrogen n-octanohydroxamate

The crystal structure and spectroscopic characteristics of n-octanohydroxamic acid and the potassium compound of that acid have been investigated by XRD, XPS, FTIR and Raman spectroscopy. XRD revealed that the acid is in the keto Z conformation with the alkyl chains oriented along the z-direction and hydrogen bonding between hydroxamate moieties. Vibrational spectra confirm this conclusion. Chemical analysis, XRD and XPS established that the potassium compound is the acid salt KH(C₇H₉CONO)₂. The crystal structure showed that the hydroxamate groups are also in the keto Z conformation and this is supported by vibrational spectra. In the acid salt, the two hydroxamate moieties are connected by a symmetrical O-H-O short hydrogen bonded linkage between the two hydroxamate oxygen atoms and this explains the absence of a discernible O-H stretch band in the vibrational spectra. Identification of the vibrational bands displayed is supported by deuteration and ¹⁵N substitution.     

Critical comparison of consensus methods for molecular sequences.

Consensus methods are recognized as valuable tools for data analysis, especially when some sort of data aggregation is desired. Although consensus methods for sequences play a vital role in molecular biology, researchers pay little heed to the features and limitations of such methods, and so there are risks that criteria for constructing consensus sequences will be misused or misunderstood. To understand better the issues involved, we conducted a critical comparison of nine consensus methods for sequences, of which eight were used in papers appearing in this journal. We report the results of that comparison, and we make recommendations which we hope will assist researchers when they must select particular consensus methods for particular applications.     

A formalization of consensus index methods

A consensus in dex method comprises a consensus method and a consensus index that are defined on a common set of objects (e.g. classifications). For each profile of objects, the consensus method returns a consensus object representing information or structure shared among profile objects, while the consensus index returns a quantitative measure of agreement among profile objects. Since the relationship between consensus method and consensus index is poorly understood, we propose simple axioms prescribing it in the most general terms. Many taxonomic consensus index methods violate these axioms because their consensus indices measure consensus object invariants rather than profile agreement. We propose paradigms to obtain consensus index methods that measure agreement and satisfy the axioms. These paradigms salvage concepts underlying consensus index methods violating the axioms. This work was supported in part by the Faculty of Science at Memorial University of Newfoundland, and by the Natural Sciences and Engineering Research Council of Canada Under Grant A-4142.     

Ghrelin O-acyltransferase (GOAT) has a preference for n-hexanoyl-CoA over n-octanoyl-CoA as an acyl donor

Ghrelin is a peptide hormone in which serine 3 is modified by n-octanoic acid through GOAT (ghrelin O-acyltransferase). However, the enzymological properties of GOAT remain to be elucidated. We analyzed the in vitro activity of GOAT using the recombinant enzyme. Unexpectedly, although the main active form of ghrelin is modified by n-octanoic acid, GOAT had a strong preference for n-hexanoyl-CoA over n-octanoyl-CoA as an acyl donor. Moreover, a four-amino acid peptide derived from the N-terminal sequence of ghrelin can be modified by GOAT, indicating that these four amino acids constitute the core motif for substrate recognition by the enzyme.     

An infrared-spectroscopic study of reversed micellar solutions of sodium n-octanoate and water in n-decanol

The association process to reversed micelles in the system water/sodium n-octanoate/n-decanol is studied by means of wave number shifts in the fundamental infrared region. It is found that the antisymmetric vibration band (σ₃), and the scissors vibration band (σ₂) of water, together with the antisymmetric stretching vibration band of the ionised carboxylic groups (σ_COO?) are capable of detecting and visualising changes in the micellar association equilibria. The information is primarily qualitative, but some rough quantitative estimations are also made. A comparison between the intensities of the narrow σ₃-line corresponding to unassociated water OH-oscillators discernible at high dilutions in decanol, and the broad σ₃-band of the associated species reveals that the fraction of unassociated OH-groups in water is low, perhaps only a few percent.     

n-3 PUFA and lipotoxicity

Excess lipid accumulation in nonadipose tissues may occur in the setting of high levels of plasma free fatty acids or triglycerides (TGs) in a process called “lipotoxicity”. Evidence from human studies and animal models suggests that lipid accumulation in the heart, skeletal muscle, pancreas, and liver play an important role in the pathogenesis of heart failure, obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). During the past few years, several studies have shown that n-3 polyunsaturated fatty acids (PUFA) have potentially cardioprotective effects, especially in high-risk patients with dyslipidemia, and might therefore be expected to be of benefit in T2DM. Moreover, new information has demonstrated the beneficial effects of consuming n-3 PUFA in preventing the complications of lipotoxicity. n-3 PUFA dietary intake thus had positive effects on fatty liver in patients with non-alcoholic fatty liver disease (NAFLD), with an improvement in liver echotexture and a significant regression of hepatic brightness, associated with improved liver hemodynamics. The n-3 PUFA also had beneficial effects on ectopic fat accumulation inside the heart, with stabilization of cardiac myocytes and antiarrhythmic effects. On the other hand, recent data from animal models suggest that oral dosing of eicosapentaenoic acid (EPA) could contribute to protect against β-cell lipotoxicity. This review discusses the latest hypotheses regarding lipotoxicity, concentrating on the impact of the n-3 PUFA that contribute to ectopic lipid storage, affecting organ function. Further human studies are needed to test the evidence and elucidate the mechanisms involved in this process.     

Regulation of n-acetylglucosamine uptake in yeast

Various yeasts have been investigated for their ability to grow on N-acetylglucosamine as the sole carbon source and only those which are associated with the disease, candidiasis, gave positive results. The yeasts unable to grow on N-acetylglucosamine lacked the capacity to transport the aminosugar across the cell membrane. In pathogenic yeasts, two systems of different affinity for substrate were found to operate in the uptake of N-acetylglucosamine. In glucose-grown cells a constitutive, low affinity uptake system was present, but upon addition of inducer, a specific high affinity uptake system was synthesized. Experiments with the inhibitors of macromolecule synthesis suggested that the synthesis of RNA and protein is necessary for induction whereas the synthesis of DNA is not.In glucose-grown Candida albicans cells which are devoid of N-acetylglucosamine enters into the cells as phosphorylated form using a constitutive uptake system. Uranyl acetate (0.01 mM) which binds to cell membrane-associated polyphosphates, inhibited completely the inducible uptake of N-acetylglucosamine. Labelling experiments, designed to determine the temporal sequence of appearance of N-acetylglucosamine in intracellular free sugar and sugar-phosphate pools, indicated that N-acetylglucosamine first appeared in the cells as phosphorylated form. Similar results were obtained with Saccharomyces cerevisiae 3059 and some other yeasts which are devoid of N-acetylglucosamine kinase in both uninduced and induced conditions. These results are consistent with the model of van Steveninck that involves phosphorylation during transport. Furthermore, inhibitors of energy metabolism (arsenate, azide and cyanide), proton conductor (m-chlorocarbonylcyanide phenylhydrazine) and dibenzyl diammonium ion (membrane permeable cation) inhibited the inducible N-acetylglucosamine uptake in C. albicans.     

Evaluation of consensus methods in predictive species distribution modelling

Aim  Spatial modelling techniques are increasingly used in species distribution modelling. However, the implemented techniques differ in their modelling performance, and some consensus methods are needed to reduce the uncertainty of predictions. In this study, we tested the predictive accuracies of five consensus methods, namely Weighted Average (WA), Mean(All), Median(All), Median(PCA), and Best, for 28 threatened plant species.
Location  North-eastern Finland, Europe.
Methods  The spatial distributions of the plant species were forecasted using eight state-of-the-art single-modelling techniques providing an ensemble of predictions. The probability values of occurrence were then combined using five consensus algorithms. The predictive accuracies of the single-model and consensus methods were assessed by computing the area under the curve (AUC) of the receiver-operating characteristic plot.
Results  The mean AUC values varied between 0.697 (classification tree analysis) and 0.813 (random forest) for the single-models, and from 0.757 to 0.850 for the consensus methods. WA and Mean(All) consensus methods provided significantly more robust predictions than all the single-models and the other consensus methods.
Main conclusions  Consensus methods based on average function algorithms may increase significantly the accuracy of species distribution forecasts, and thus they show considerable promise for different conservation biological and biogeographical applications.     

The equilibrium and stability for n alleles under the density-dependent selection

The problem of the equilibrium under the density-dependent selection for n-alleles belonging to one locus is considered. The new “measure of quality” of the population φ is introduced and it is shown that the equilibrium points are the constrained stationary points of the function φ and all locally stable equilibriums are its local maximum points. The analoque of the Fisher theorem for density-dependent selection is considered.     

Orthorhombic n-octadecanol: An electron diffraction study

Electron diffraction and image data on the orthorhombic β polymorph of n-octadecanol are used to deduce its crystal structure. Intensity data from the (001) projection indicate the crystals to be less bent than many other microcrystalline long chain materials. This can be explained by infinite hydrogen bond chains in the polar region which bind monolayers together. Selective sublimation of the microcrystals along the crystallographic b axis in vacuo indicates the hydrogen bonds to run parallel to the long a-axis, as was also found in X-ray studies of the monoclinic γ-polymorph. The presence of electron diffraction reflections forbidden by O₁ subcell symmetry does not indicate another β polymorph, as suggested by other workers, but is due to the well-characterized phenomenon of multiple elastic scattering from layered structures.     

Isolation of n-paraffins and sec-alcohols from Isotachis japonica

Two homologous series of n-paraffins and sec-alcohols from C₂₀ to C₃₄ or C₃₅ were isolated a wax constituents of a liverwort, Isotachis japonica. In both series, odd-members were predominant compared with even-members: the ratio of the total amount of odd- to total amounts of even-members was 3·9 in the n-paraffin homologues, and 16·5 in the sec-alcohol homologues.     

Spectroscopic characterisation of copper acetohydroxamate and copper n-octanohydroxamate

The nature of the bonding in acetohydroxamic acid, copper acetohydroxamate and copper n-octanohydroxamate has been investigated by chemical analysis, XPS, FTIR and Raman spectroscopy. Vibrational spectra show the acid to be in the keto Z conformation as was previously established for the n-octano homologue. Chemical analysis established that the copper compounds have a copper:hydroxamate stoichiometry of 1:1. XPS confirms that they are Cu^II compounds. The absence of vibrational spectral bands that were previously identified with N-H vibrations for n-octanohydroxamic acid and its potassium compound, together with the presence of a CN stretch band that shifts when the nitrogen is labelled with ¹⁵N, confirms that the hydroxamate moieties in the Cu^II compounds are in the enol configuration. Some interaction between Cu and N is indicated by the spectra and could explain the 1:1 stoichiometry of the Cu^II hydroxamates investigated.     

The pathway from arachidonic to docosapentaenoic acid (20:4n-6 to 22:5n-6) and from eicosapentaenoic to docosahexaenoic acid (20:5n-3 to 22:6n-3) studied in testicular cells from immature rats

The concentration-dependent metabolism of 1-¹⁴C-labelled precursors of 22:5n-6 and 22:6n-3 was compared in rat testis cells. The amounts of [¹⁴C]22- and 24-carbon metabolites were measured by HPLC. The conversion of [1-¹⁴C]20:5n-3 to [3-¹⁴C]22:6n-3 was more efficient than that of [1-¹⁴C]20:4n-6 to [3-¹⁴C]22:5n-6. At low substrate concentration (4 μM) it was 3.4 times more efficient, reduced to 2.3 times at high substrate concentration (40 μM). The conversion of [1-¹⁴C]22:5n-3 to [1-¹⁴C]22:6n-3 was 1.7 times more efficient than that of [1-¹⁴C]22:4n-6 to [1-¹⁴C]22:5n-6 using a low, but almost equally efficient using a high substrate concentration. When unlabelled 20:5n-3 was added to a cell suspension incubated with [1-¹⁴C]20:4n-6 or unlabelled 22:5n-3 to a cell suspension incubated with [1-¹⁴C]22:4n-6, the unlabelled n-3 fatty acids strongly inhibited the conversion of [1-¹⁴C]20:4n-6 or [1-¹⁴C]22:4n-6 to [¹⁴C]22:5n-6. In the reciprocal experiment, unlabelled 20:4n-6 and 22:4n-6 only weakly inhibited the conversion of [1-¹⁴C]20:5n-3 and [1-¹⁴C]22:5n-3 to [¹⁴C]22:6n-3. The results indicate that if both n-6 and n-3 fatty acids are present, the n-3 fatty acids are preferred over the n-6 fatty acids in the elongation from 20- to 22- and from 22- to 24-carbon atom fatty acids. In vivo the demand for 22-carbon fatty acids for spermatogenesis in the rat may exceed the supply of n-3 precursors and thus facilitate the formation of 22:5n-6 from the more abundant n-6 precursors.     

ArrayMining: a modular web-application for microarray analysis combining ensemble and consensus methods with cross-study normalization

Background  

Statistical analysis of DNA microarray data provides a valuable diagnostic tool for the investigation of genetic components of diseases. To take advantage of the multitude of available data sets and analysis methods, it is desirable to combine both different algorithms and data from different studies. Applying ensemble learning, consensus clustering and cross-study normalization methods for this purpose in an almost fully automated process and linking different analysis modules together under a single interface would simplify many microarray analysis tasks.     

Interactions between diacylglycerophosphoethanolamines and n-alkanes in monolayers and bilayers

Surface pressure-area isotherms of l-diacylglycerophosphoethanolamines were measured at the n-alkane/water interfaces for alkanes ranging from n-hexane to n-hexadecane. Transition pressures from the expanded film to the condensed state varied largely depending on the chain length of the n-alkane in the oil phase. The phase transition temperature and the entropy were studied by differential scanning calorimetry in presence of n-alkanes for the same lipid. The temperatures of gel-to-liquid crystalline phase transitions were changed in the same way as the monolayers reflecting the chain lengths of the n-alkanes present. The effects of the n-alkanes on monolayers and bilayers were entirely parallel; they are discussed taking the mixing of the lipids and the n-alkanes into account in the condensed films for the former and in the gel phase for the latter.