Pathological Metabolism of Methionine in Malignant Cells Is a Potential Target for the Antitumor Therapy

This review presents the characteristics of the cellular metabolism of methionine, as well as known data on the mechanisms of the development of methionine dependence in malignant cells. The possibilities of using a non-methionine diet for the control of the tumor growth in patients with various forms of cancer are considered. The newest information about methionine-γ-lyase, an enzyme providing elimination of methionine from plasma, is grouped and summarised. Its role as a potential antitumor enzyme is disclosed. Data on methionine-γ-lyase producers, activity of this enzyme, obtained from various sources, and information on tumor models and cell cultures, showing methionine dependence are summarised

A Parsimony Approach to Biological Pathway Reconstruction/Inference for Genomes and Metagenomes

A common biological pathway reconstruction approach—as implemented by many automatic biological pathway services (such as the KAAS and RAST servers) and the functional annotation of metagenomic sequences—starts with the identification of protein functions or families (e.g., KO families for the KEGG database and the FIG families for the SEED database) in the query sequences, followed by a direct mapping of the identified protein families onto pathways. Given a predicted patchwork of individual biochemical steps, some metric must be applied in deciding what pathways actually exist in the genome or metagenome represented by the sequences. Commonly, and straightforwardly, a complete biological pathway can be identified in a dataset if at least one of the steps associated with the pathway is found. We report, however, that this naïve mapping approach leads to an inflated estimate of biological pathways, and thus overestimates the functional diversity of the sample from which the DNA sequences are derived. We developed a parsimony approach, called MinPath (Minimal set of Pathways), for biological pathway reconstructions using protein family predictions, which yields a more conservative, yet more faithful, estimation of the biological pathways for a query dataset. MinPath identified far fewer pathways for the genomes collected in the KEGG database—as compared to the naïve mapping approach—eliminating some obviously spurious pathway annotations. Results from applying MinPath to several metagenomes indicate that the common methods used for metagenome annotation may significantly overestimate the biological pathways encoded by microbial communities

Intrinsic Determinants of Aβ12–24 pH-Dependent Self-Assembly Revealed by Combined Computational and Experimental Studies

The propensity of amyloid- (A) peptide to self-assemble into highly ordered amyloid structures lies at the core of their accumulation in the brain during Alzheimer's disease. By using all-atom explicit solvent replica exchange molecular dynamics simulations, we elucidated at the atomic level the intrinsic determinants of the pH-dependent dimerization of the central hydrophobic segment A and related these with the propensity to form amyloid fibrils measured by experimental tools such as atomic force microscopy and fluorescence. The process of A dimerization was evaluated in terms of free energy landscape, side-chain two-dimensional contact probability maps, -sheet registries, potential mean force as a function of inter-chain distances, secondary structure development and radial solvation distributions. We showed that dimerization is a key event in A amyloid formation; it is highly prompted in the order of pH 5.02.98.4 and determines further amyloid growth. The dimerization is governed by a dynamic interplay of hydrophobic, electrostatic and solvation interactions permitting some variability of -sheets at each pH. These results provide atomistic insight into the complex process of molecular recognition detrimental for amyloid growth and pave the way for better understanding of the molecular basis of amyloid diseases

CRISPR-based strategies in infectious disease diagnosis and therapy

CRISPR gene-editing technology has the potential to transform the diagnosis and treatment of infectious diseases, but most clinicians are unaware of its broad applicability. Derived from an ancient microbial defence system, these so-called "molecular scissors" enable precise gene editing with a low error rate. However, CRISPR systems can also be targeted against pathogenic DNA or RNA sequences. This potential is being combined with innovative delivery systems to develop new therapeutic approaches to infectious diseases.info:eu-repo/semantics/publishedVersio

LNCaP Atlas: Gene expression associated with in vivo progression to castration-recurrent prostate cancer

<p>Abstract</p> <p>Background</p> <p>There is no cure for castration-recurrent prostate cancer (CRPC) and the mechanisms underlying this stage of the disease are unknown.</p> <p>Methods</p> <p>We analyzed the transcriptome of human LNCaP prostate cancer cells as they progress to CRPC <it>in vivo </it>using replicate LongSAGE libraries. We refer to these libraries as the LNCaP atlas and compared these gene expression profiles with current suggested models of CRPC.</p> <p>Results</p> <p>Three million tags were sequenced using <it>in vivo </it>samples at various stages of hormonal progression to reveal 96 novel genes differentially expressed in CRPC. Thirty-one genes encode proteins that are either secreted or are located at the plasma membrane, 21 genes changed levels of expression in response to androgen, and 8 genes have enriched expression in the prostate. Expression of 26, 6, 12, and 15 genes have previously been linked to prostate cancer, Gleason grade, progression, and metastasis, respectively. Expression profiles of genes in CRPC support a role for the transcriptional activity of the androgen receptor (<it>CCNH, CUEDC2, FLNA, PSMA7</it>), steroid synthesis and metabolism (<it>DHCR24, DHRS7</it>, <it>ELOVL5, HSD17B4</it>, <it>OPRK1</it>), neuroendocrine (<it>ENO2, MAOA, OPRK1, S100A10, TRPM8</it>), and proliferation (<it>GAS5</it>, <it>GNB2L1</it>, <it>MT-ND3</it>, <it>NKX3-1</it>, <it>PCGEM1</it>, <it>PTGFR</it>, <it>STEAP1</it>, <it>TMEM30A</it>), but neither supported nor discounted a role for cell survival genes.</p> <p>Conclusions</p> <p>The <it>in vivo </it>gene expression atlas for LNCaP was sequenced and support a role for the androgen receptor in CRPC.</p

Major prospects for exploring canine vector borne diseases and novel intervention methods using 'omic technologies

Canine vector-borne diseases (CVBDs) are of major socioeconomic importance worldwide. Although many studies have provided insights into CVBDs, there has been limited exploration of fundamental molecular aspects of most pathogens, their vectors, pathogen-host relationships and disease and drug resistance using advanced, 'omic technologies. The aim of the present article is to take a prospective view of the impact that next-generation, 'omics technologies could have, with an emphasis on describing the principles of transcriptomic/genomic sequencing as well as bioinformatic technologies and their implications in both fundamental and applied areas of CVBD research. Tackling key biological questions employing these technologies will provide a 'systems biology' context and could lead to radically new intervention and management strategies against CVBDs