A case–control study on the effect of metabolic gene polymorphisms, nutrition, and their interaction on the risk of non-alcoholic fatty liver disease

The oxidative stress is a key issue in the etiology of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to evaluate the effect of metabolic gene polymorphisms involved in the oxidative stress (GSTT1, GSTM1, SULT1A1, CYP2E1, and 1A1), lifestyle and nutrition aspects, and their interaction, on the risk of NAFLD. We enrolled 294 cases and 359 controls, and collected demographics, anthropometric, lifestyle, and nutrition data. A subgroup of NAFLD provided additional data on nutrients and on physical activity engagement. Each patient provided a blood sample for DNA extraction and genotyping. Clinical and laboratory data were collected from cases. Multivariable analysis shows a significant protective effect of age, gender, and moderate drinking habits on the risk of NAFLD, while an increased risk for greater consumption of fruit and grilled meat or fish. Significant interactions were reported between alcohol consumption, fruit intake, grilled meat and fish, and selected genetic variants. From the subgroup analysis, a moderate/high consumption of fat and/or grilled meat/fish, and a high consumption of white meat increase the risk of NAFLD. Engaging any physical activity at least 1 time/week halves the risk of NAFLD. Besides confirming the beneficial effect of moderate alcohol intake and regular physical activity, and the increased risk associated with high fruit and fat intake, for the first time, we report a detrimental effect of grilled food on NAFLD risk. An effect modification by selected gene variants increases the risk in combination with fruit and grilled food intake.     

New biologically active epidioxysterols from Stereum hirsutum

From the fungus Stereum hirsutum have been isolated and identified two new epidioxysterols 1, 4, together with two known ones 2 and 3. Their structures were elucidated on the basis of spectroscopic analysis and chemical reactions. Epidioxysterols 1-4 have been shown to possess a significant activity against Mycobacterium tuberculosis.     

Monitoring of cross-country skiers by means of an expert model of potential performance

On the basis of expert knowledge, an expert model of potential performance covering the motor, morphological, psychological, and sociological subspace was constructed (MMPS). The scores of variables were obtained by application of the computer program Sport Measurement Management System (SMMS). In the subjects included in measurements, trends of the obtained average scores of variables were established through various competition categories and age periods. The sample of subjects consisted of 48 cross-country skiers in three competition categories. Fluctuations in development in individual age periods are larger in the motor and morphological subspace. In the psychological subspace, an upward trend of average scores can be noticed, while the sociological subspace is not subjected to any essential changes in different age and competition categories. Monitoring of cross-country skiers across all three competition categories showed that in these age categories there are periods which owing to laws of development do not allow uniform progress. Therefore, the principle of individuality must be taken into account especially in planning the transformation process.     

Sequence signatures of direct complementarity between mRNAs and cognate proteins on multiple levels

A potential connection between physico-chemical properties of mRNAs and cognate proteins, with implications concerning both the origin of the genetic code and mRNA–protein interactions, is unexplored. We compare pyrimidine content of naturally occurring mRNA coding sequences with the propensity of cognate protein sequences to interact with pyrimidines. The latter is captured by polar requirement, a measure of solubility of amino acids in aqueous solutions of pyridines, heterocycles closely related to pyrimidines. We find that the higher the pyrimidine content of an mRNA, the stronger the average propensity of its cognate protein’s amino acids to interact with pyridines. Moreover, window-averaged pyrimidine profiles of individual mRNAs strongly mirror polar-requirement profiles of cognate protein sequences. For example, 4953 human proteins exhibit a correlation between the two with |R| > 0.8. In other words, pyrimidine-rich mRNA regions quantitatively correspond to regions in cognate proteins containing residues soluble in pyrimidine mimetics and vice versa. Finally, by studying randomized genetic code variants we show that the universal genetic code is highly optimized to preserve these correlations. Overall, our findings redefine the stereo-chemical hypothesis concerning code’s origin and provide evidence of direct complementary interactions between mRNAs and cognate proteins before development of ribosomal decoding, but also presently, especially if both are unstructured.     

Computational analysis of amino acids and their sidechain analogs in crowded solutions of RNA nucleobases with implications for the mRNA–protein complementarity hypothesis

Many critical processes in the cell involve direct binding between RNAs and proteins, making it imperative to fully understand the physicochemical principles behind such interactions at the atomistic level. Here, we use molecular dynamics simulations and 15 μs of sampling to study the behavior of amino acids and amino acid sidechain analogs in high-concentration aqueous solutions of standard RNA nucleobases. Structural and energetic analysis of simulated systems allows us to derive interaction propensity scales for different amino acid/nucleobase combinations. The derived scales closely match and greatly extend the available experimental data, providing a comprehensive foundation for studying RNA–protein interactions in different contexts. By using these scales, we demonstrate a statistically significant connection between nucleobase composition of human mRNA coding sequences and nucleobase interaction propensities of their cognate protein sequences. For example, pyrimidine density profiles of mRNAs match uracil-propensity profiles of their cognate proteins with a median Pearson correlation coefficient of R = −0.70. Our results provide support for the recently proposed hypotheses that mRNAs and their cognate proteins may be physicochemically complementary to each other and bind, especially if unstructured, with the complementarity level being negatively influenced by mRNA adenine content. Finally, we utilize the derived scales to refine the complementarity hypothesis and closely examine its physicochemical underpinnings.     

Histone modifications as a platform for cancer therapy

Tumorigenesis and metastasis are a progression of events resulting from alterations in the processing of the genetic information. These alterations result from stable genetic changes (mutations) involving tumor suppressor genes and oncogenes (e.g., ras, BRAF) and potentially reversible epigenetic changes, which are modifications in gene function without a change in the DNA sequence. Mutations of genes coding for proteins that directly or indirectly influence epigenetic processes will alter the cell's gene expression program. Epigenetic mechanisms often altered in cancer cells are DNA methylation and histone modifications (acetylation, methylation, phosphorylation). This article will review the potential of these reversible epigenetic processes as targets for cancer therapies.