Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room

A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69–0.99) and a specificity 0.84 (95% CI 0.58–0.94) with an AUC of 0.93 (95% CI 0.89–1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85–1.00) and specificity of 0.95 (95% CI 0.74–0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.     

Comparative study of the microtriches of adult Cestodes (Proteocephalidea: Monticelliidae), and some comments on their systematic value

The surface of the tegument of the scolex and the immature proglottides of Monticellia belavistensis, M. ventrei, Nomimoscolex chubbi, and N. lopesi is described using scanning electron microscopy. Only blade-like spiniform microtriches and filiform microtriches were observed in the species studied. The types, size and density of microtriches on the apical region surface of the scolex, central cavity surface of suckers, marginal ring surface of suckers, non-adherent surface of suckers, proliferation zone surface, and immature proglottis surface were compared among these species. The distribution pattern of the microtriches was not a reliable feature to discriminate among the genera considered in this study. It varied in each of the species of Monticellia examined, and did not permit to split the heterogeneous genus Nomimoscolex. However, the microthrix pattern can be regarded as an additional diagnostic feature to distinguish among species of proteocephalideans. Further comparative research involving other species of proteocephalid taxa is needed to elucidate the systematic value of the tegumental morphology.     

Ultrastructure of the developing pigment strand of rice (Oryza sativa L.) in relation to its role in solute transport

Summary The developing pigment strand of rice (Oryza sativa L.) was studied by conventional electron microscopy and also by use of thick sections post-fixed with zinc iodide and osmium (ZIO).When the rice caryopsis achieves maximum length, a suberised adcrusting wall layer is laid down over the original primary walls of the pigment strand. Concomitant with suberin deposition a proliferation of tubular endoplasmic reticulum occurs in the cytoplasm giving rise to numerous interconnected vesicles which bear ribosomes. The vesicles in the general cytoplasm retain their ribosomes while those close to the wall become smooth and contain an electron-opaque granular material which is eventually deposited to the outside of the plasmalemma. This granular material may be the precursor(s) from which suberin is polymerised. The suberised wall attains about six times the width of the original primary wall and plasmodesmata, which traverse both primary wall and suberised wall layers, become greatly elongated.Lipid bodies increase in both size and frequency during development, eventually coalescing to form a complete plug across the pigment strand and occluding the symplast of this tissue. The significance of these ultrastructural observations is discussed in relation to the previously demonstrated role of the pigment strand as a translocation pathway for water and assimilates during grain filling.Abbreviations ER endoplasmic reticulum - ZIO zinc iodide-osmium fixation     

What Can We Learn from the Evolution of Protein-Ligand Interactions to Aid the Design of New Therapeutics?

Efforts to increase affinity in the design of new therapeutic molecules have tended to lead to greater lipophilicity, a factor that is generally agreed to be contributing to the low success rate of new drug candidates. Our aim is to provide a structural perspective to the study of lipophilic efficiency and to compare molecular interactions created over evolutionary time with those designed by humans. We show that natural complexes typically engage in more polar contacts than synthetic molecules bound to proteins. The synthetic molecules also have a higher proportion of unmatched heteroatoms at the interface than the natural sets. These observations suggest that there are lessons to be learnt from Nature, which could help us to improve the characteristics of man-made molecules. In particular, it is possible to increase the density of polar contacts without increasing lipophilicity and this is best achieved early in discovery while molecules remain relatively small.     

N-Acetylsuccinimidylglutamate, a Cyclic Imide Form of the Peptide N-Acetylaspartylglutamate, Is Present in Low Micromolar Concentrations in Murine and Bovine CNS

Abstract: N -Acetylsuccinimidylglutamate [(asu)NAAG], a cyclic form of the peptide N -acetylaspartylglutamate (NAAG) in which the aspartyl residue is linked to glutamate via the α- and β-carboxylates, was identified and quantified by HPLC in the murine and bovine CNS. In the rat, the highest concentrations of (asu)NAAG were detected in the spinal cord (1.83 ± 0.15 pmol/mg of wet tissue weight) and brainstem (1.16 ± 0.08 pmol/mg wet weight), whereas the levels were below the limit of detection in cerebellum, hippocampus, and cerebral cortex. (Asu)NAAG was also detected in significant amounts in the superior colliculus and lateral genicutale nucleus (1.17 ± 0.05 and 0.82 ± 0.13 pmol/mg wet weight, respectively). Although the tissue content of (asu)NAAG was about three orders of magnitude lower than that of NAAG, levels of both peptides were positively correlated among different CNS regions ( r = 0.74, p < 0.003). In the rat spinal cord, (asu)NAAG levels progressively increased from week 2 to month 12 after birth. In bovine spinal cord, the contents of (asu)NAAG and NAAG were comparable in gray and white matter as well as in the dorsal and ventral horns. These results suggest that NAAG and (asu)-NAAG are closely related metabolically and raise the question of the physiological significance of such a cyclic peptide.     

Nitrogen Oxyanion-dependent Dissociation of a Two-component Complex That Regulates Bacterial Nitrate Assimilation

Nitrogen is an essential nutrient for growth and is readily available to microbes in many environments in the form of ammonium and nitrate. Both ions are of environmental significance due to sustained use of inorganic fertilizers on agricultural soils. Diverse species of bacteria that have an assimilatory nitrate/nitrite reductase system (NAS) can use nitrate or nitrite as the sole nitrogen source for growth when ammonium is limited. In Paracoccus denitrificans, the pathway-specific two-component regulator for NAS expression is encoded by the nasT and nasS genes. Here, we show that the putative RNA-binding protein NasT is a positive regulator essential for expression of the nas gene cluster (i.e. nasABGHC). By contrast, a nitrogen oxyanion-binding sensor (NasS) is required for nitrate/nitrite-responsive control of nas gene expression. The NasS and NasT proteins co-purify as a stable heterotetrameric regulatory complex, NasS-NasT. This protein-protein interaction is sensitive to nitrate and nitrite, which cause dissociation of the NasS-NasT complex into monomeric NasS and an oligomeric form of NasT. NasT has been shown to bind the leader RNA for nasA. Thus, upon liberation from the complex, the positive regulator NasT is free to up-regulate nas gene expression.