Toll-like receptor 4 deficiency: Smaller infarcts,but nogain in function

Backgound  

It has been reported that Toll-like receptor 4 (TLR4) deficiency reduces infarct size after myocardial ischemia/reperfusion (MI/R). However, measurement of MI/R injury was limited and did not include cardiac function. In a chronic closed-chest model we assessed whether cardiac function is preserved in TLR4-deficient mice (C3H/HeJ) following MI/R, and whether myocardial and systemic cytokine expression differed compared to wild type (WT).     

State-of-the art data normalization methods improve NMR-based metabolomic analysis

Extracting biomedical information from large metabolomic datasets by multivariate data analysis is of considerable complexity. Common challenges include among others screening for differentially produced metabolites, estimation of fold changes, and sample classification. Prior to these analysis steps, it is important to minimize contributions from unwanted biases and experimental variance. This is the goal of data preprocessing. In this work, different data normalization methods were compared systematically employing two different datasets generated by means of nuclear magnetic resonance (NMR) spectroscopy. To this end, two different types of normalization methods were used, one aiming to remove unwanted sample-to-sample variation while the other adjusts the variance of the different metabolites by variable scaling and variance stabilization methods. The impact of all methods tested on sample classification was evaluated on urinary NMR fingerprints obtained from healthy volunteers and patients suffering from autosomal polycystic kidney disease (ADPKD). Performance in terms of screening for differentially produced metabolites was investigated on a dataset following a Latin-square design, where varied amounts of 8 different metabolites were spiked into a human urine matrix while keeping the total spike-in amount constant. In addition, specific tests were conducted to systematically investigate the influence of the different preprocessing methods on the structure of the analyzed data. In conclusion, preprocessing methods originally developed for DNA microarray analysis, in particular, Quantile and Cubic-Spline Normalization, performed best in reducing bias, accurately detecting fold changes, and classifying samples.

     

Effect of oleocellosis,desiccation, and fungal infection upon the terpenes of individual oil glands in Citrus latipes

Mono- and sesqui-terpenes of individual oil glands of Citrus latipes fruits were analyzed for their homogeneity. The effect of oleocellosis, desiccation, Penicillium and Phytophthora infection upon the individual terpene components was investigated and expressed in a discriminant analysis and in canonical variables. Each oil gland contained the entire spectrum of terpenes specific for each species, and the biggest difference in affected glands was due to Penicillium infection.     

Anions permeate and gate GCAC1, a voltage-dependent guard cell anion channel

GCAC1 is a strongly voltage-dependent anion channel in the guard-cell plasma membrane of Vicia faba . In patch–clamp experiments, we have investigated the permeation and gating properties of GCAC1 with respect to its anion dependence in the whole-cell and excised-patch configuration. The relative permeability followed the order SCN^– > NO₃^– > Br^– > Cl^–, while the single-channel conductances in symmetrical anionic solutions exhibited a nearly inverse sequence. The Cl^– dependence of inward currents (Cl^– release) is characterized by a maximum single-channel conductance of 89 pS half-saturating at 87 mM cytoplasmic chloride. In addition to this substrate saturation, anion release was also dependent on the external Cl^– activity ( K _m = 16 mM). In the presence of SCN^– and Cl^–, the single-channel conductance exhibited an anomalous mole-fraction dependence, identifying GCAC1 as a multi-ion single-file pore. Using anions with increasing ionic size, a minimum pore diameter of 0.5 nm was assumed from their relative permeabilities. In line with an anion-selective channel, a tenfold increase in the extracellular anion activity shifted the reversal potential by –59.8 mV. Simultaneously, the half-activation potential shifted negatively by about 23 mV. A further analysis of the anion dependence revealed that extracellular rather than cytosolic anions affect the gating process of GCAC1. From anion substitution experiments, we conclude that anion concentration and species determines both permeation and gating of the plant anion channel GCAC1.     

Combined UV and Liquid Scintillation Detection in HPLC. Formation and Depurination of Substitution Inert Pt(II) Complexes of Purine Nucleosides

Abstract

Combined UV- and liquid scintillation-HPLC has been applied to study the complexing of purine nucleosides with Pt(II)-diamine ions, and the effect of the complex formation on the acidic depurination.     

Identifying essential genes in bacterial metabolic networks with machine learning methods

Background  

Identifying essential genes in bacteria supports to identify potential drug targets and an understanding of minimal requirements for a synthetic cell. However, experimentally assaying the essentiality of their coding genes is resource intensive and not feasible for all bacterial organisms, in particular if they are infective.     

Modulatory effect of guanosine-3':5' cyclic monophosphate on macrophage susceptibility to Trypanosoma cruzi infection

The effects of agents that elevate intracellular levels of cGMP on macrophage internalization of the unicellular parasite Trypanosoma cruzi and latex particles were examined in an attempt to define characteristics of the infective process. Presence of imidazole, a drug that prevents degradation of the cGMP by inhibiting cGMP phosphodiesterase activity, during macrophage-T. cruzi interaction resulted in a marked increase in the number of parasites associated with the cells and the percentage of infected cells. Similar results were obtained when sodium nitroprusside (SNP), which increases cGMP levels by an as yet undefined mechanism, dibutyryl-cGMP, or both imidazole and dibutyryl-cGMP were added to the system. In contrast, the presence of imidazole, SNP, or dibutyryl-cGMP had no significant consequence on latex particle uptake by the macrophages. Whereas pretreatment of macrophages with imidazole plus dibutyryl-cGMP readily increased T. cruzi infection, pretreatment of the parasite with these drugs had no significant effect on the interaction. Furthermore, results of radioimmunoassays showed that imidazole and SNP indeed elevated cGMP levels in the macrophages but not in the parasites. Taken together, these results indicate that cGMP plays a facilitating role in macrophage infection by T. cruzi that contrasts with the lack of effect on the uptake of inert latex particles and the previously reported inhibitory effect of cAMP in the same system. Thus, cyclic nucleotides appear to play a role in modulating internalization of the parasite but not in the uptake of an inert particle by macrophages.     

Untersuchungen an einigen Blattfarbenmutanten der Sippe 50 vonAntirrhinum Majus L

Ohne Zusammenfassung     

Extremitätenreste einer Mönchsrobbe (Phocidae,Carnivora, Mammalia) aus dem Miozän von Bocholt (Niederrhein)

From the Reinbekian deposits of Bocholt (Lower Rhine) a left femur and the distal fragment of a left tibia are described. A comparison with known fossil specimens results no direct conformity. The morphological relationship of the limb bones is nearest to the Monachinae. They are introduced with the termMonotherium sp. Due to their stratigraphical age, in comparison to younger relations, they own some primitive features.