Fatty Acid Elongation in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma

Non-alcoholic steatohepatitis (NASH) represents a risk factor for the development of hepatocellular carcinoma (HCC) and is characterized by quantitative and qualitative changes in hepatic lipids. Since elongation of fatty acids from C16 to C18 has recently been reported to promote both hepatic lipid accumulation and inflammation we aimed to investigate whether a frequently used mouse NASH model reflects this clinically relevant feature and whether C16 to C18 elongation can be observed in HCC development. Feeding mice a methionine and choline deficient diet to model NASH not only increased total hepatic fatty acids and cholesterol, but also distinctly elevated the C18/C16 ratio, which was not changed in a model of simple steatosis (ob/ob mice). Depletion of Kupffer cells abrogated both quantitative and qualitative methionine-and-choline deficient (MCD)-induced alterations in hepatic lipids. Interestingly, mimicking inflammatory events in early hepatocarcinogenesis by diethylnitrosamine-induced carcinogenesis (48 h) increased hepatic lipids and the C18/C16 ratio. Analyses of human liver samples from patients with NASH or NASH-related HCC showed an elevated expression of the elongase ELOVL6, which is responsible for the elongation of C16 fatty acids. Taken together, our findings suggest a detrimental role of an altered fatty acid pattern in the progression of NASH-related liver disease.     

Radicals and radical ions as intermediates of electron transfer processes through peptides

Electron transfer (ET) through peptides and proteins is a key biochemical process, which involves radicals and radical ions as reactive intermediates. We have developed an assay that allows us to study this fundamental chemical reaction.     

Mechanical activation of talc in high-energy speed rotary mechanoactivator

This paper presents the results of research on mechanical activation of raw talc in a high-energy speed rotary mechanoactivator. The results of research on effect of mechanically activated talc on the degree of recovery Fe₂O₃ by hydrometallurgical method are also presented. The process and mechanism of mechanical activation in this type of mechanoactivator were achieved by impact.The variable parameters of the mechanoactivator operation were: rate of rotor revolutions (n₀ = 10,000 and n₀ = 20,000 rpm), circle sieve mesh (80, 120, 200 and 500 μm) and the current intensity. The following parameters of the dry mechanical activation process were studied: mechanical activation time, rotor speed, mechanoactivator capacity and specific energy consumption. The mechanically activated powder was examined by application of differential thermal and thermogravimetric analyses, analysis of the degree of mechanical activation and the specific surface area as well.According to the obtained results, the highest rate of mechanical activation was obtained with a nominal mechanoactivator load. The degree of mechanical activation increases with increasing the rate of rotor revolution, circle sieve mesh size and with the increasing mechanoactivator load. It was shown that high-grade talc concentrate with low content of Fe₂O₃ can be obtained by physical-chemical process. A new approach for obtaining high-grade talc concentrate was achieved trough mechanically activated talc effect on the degree of recovery of Fe₂O₃ by hydrometallurgical process.     

The intracellular Ig fold: a robust protein scaffold for the engineering of molecular recognition

Protein scaffolds that support molecular recognition have multiple applications in biotechnology. Thus, protein frames with robust structural cores but adaptable surface loops are in continued demand. Recently, notable progress has been made in the characterization of Ig domains of intracellular origin--in particular, modular components of the titin myofilament. These Ig belong to the I(intermediate)-type, are remarkably stable, highly soluble and undemanding to produce in the cytoplasm of Escherichia coli. Using the Z1 domain from titin as representative, we show that the I-Ig fold tolerates the drastic diversification of its CD loop, constituting an effective peptide display system. We examine the stability of CD-loop-grafted Z1-peptide chimeras using differential scanning fluorimetry, Fourier transform infrared spectroscopy and nuclear magnetic resonance and demonstrate that the introduction of bioreactive affinity binders in this position does not compromise the structural integrity of the domain. Further, the binding efficiency of the exogenous peptide sequences in Z1 is analyzed using pull-down assays and isothermal titration calorimetry. We show that an internally grafted, affinity FLAG tag is functional within the context of the fold, interacting with the anti-FLAG M2 antibody in solution and in affinity gel. Together, these data reveal the potential of the intracellular Ig scaffold for targeted functionalization.     

A Decision Tree Approach for Predicting Smokers' Quit Intentions

This paper presents a decision treeapproach for predicting smokers' quit intentions usingthe data from the International Tobacco Control FourCountry Survey. Three rule-based classification modelsare generated from three data sets using attributes inrelation to demographics, warning labels, and smokers'beliefs. Both demographic attributes and warning labelattributes are important in predicting smokers' quitintentions. The model's ability to predict smokers' quitintentions is enhanced, if the attributes regardingsmokers' internal motivation and beliefs about quittingare included.     

Fragmentation and bond strength of airborne diesel soot agglomerates

Background  

The potential of diesel soot aerosol particles to break up into smaller units under mechanical stress was investigated by a direct impaction technique which measures the degree of fragmentation of individual agglomerates vs. impact energy. Diesel aerosol was generated by an idling diesel engine used for passenger vehicles. Both the aerosol emitted directly and aerosol that had undergone additional growth by Brownian coagulation ("aging") was investigated. Optionally a thermo-desoption technique at 280°C was used to remove all high-volatility and the majority of low-volatility HC adsorbates from the aerosol before aging.     

Total synthesis and initial structure-activity relationships of longicatenamycin A

Natural products have provided the majority of lead structures for marketed antibacterials. In addition, they are biological guide principles to new therapies. Nevertheless, numerous "old" classes of antibiotics such as the longicatenamycins have never been explored by chemical postevolution. Longicatenamycin A is the first defined longicatenamycin congener that has been totally synthesized and tested in pure form. This venture required the de novo syntheses of the non-proteinogenic amino acids (2S,3R)-beta-hydroxyglutamic acid (HyGlu), 5-chloro-D-tryptophan (D-ClTrp), and (S)-2-amino-6-methylheptanoic acid (hhLeu). In the key step, the sensitive HyGlu building block was coupled as a pentafluorophenyl active ester to the unprotected H-D-ClTrp-Glu-hhLeu-D-Val-D-(Cbz)Orn-OH fragment. This first total synthesis of longicatenamycin A provided new congeners of the natural product (deacetyllongicatenamycin, dechlorolongicatenamycin, and longicatenamycin-A-amide).     

Evaluation of linear Kalman filter processing geodetic kinematic measurements

The purpose of this paper is to assess the efficiency of the linear Kalman filter as a method for the estimation of kinematic process observed with electronic tacheometer. On the assumption that the kinematic process is observed with only one measurement system there is no redundancy of the measurements. For evaluation of the unknown system state and its statistics in real time, other methods such as filters have to be used instead of classical geodetic adjustment. In this contribution, the efficiency of the three-dimensional linear Kalman filter model, i.e., continuous Wiener process acceleration model, in combination with the law on transfer of variances and covariances, is controlled using a known reference trajectory and statistical tests. The results of numerical tests confirmed the appropriateness of the model to evaluate geodetic kinematic measurements, where no redundant observations are available.     

Universally applicable model for the quantitative determination of lake sediment composition using fourier transform infrared spectroscopy

Fourier transform infrared spectroscopy (FTIRS) can provide detailed information on organic and minerogenic constituents of sediment records. Based on a large number of sediment samples of varying age (0-340,000 yrs) and from very diverse lake settings in Antarctica, Argentina, Canada, Macedonia/Albania, Siberia, and Sweden, we have developed universally applicable calibration models for the quantitative determination of biogenic silica (BSi; n = 816), total inorganic carbon (TIC; n = 879), and total organic carbon (TOC; n = 3164) using FTIRS. These models are based on the differential absorbance of infrared radiation at specific wavelengths with varying concentrations of individual parameters, due to molecular vibrations associated with each parameter. The calibration models have low prediction errors and the predicted values are highly correlated with conventionally measured values (R = 0.94-0.99). Robustness tests indicate the accuracy of the newly developed FTIRS calibration models is similar to that of conventional geochemical analyses. Consequently FTIRS offers a useful and rapid alternative to conventional analyses for the quantitative determination of BSi, TIC, and TOC. The rapidity, cost-effectiveness, and small sample size required enables FTIRS determination of geochemical properties to be undertaken at higher resolutions than would otherwise be possible with the same resource allocation, thus providing crucial sedimentological information for climatic and environmental reconstructions.