Association between plasma angiotensin-converting enzyme level and radiation pneumonitis

Angiotensin-converting enzyme (ACE) plays an important role in pulmonary fibrosis and may be involved in the development of radiation-induced lung damage. The objective of this study was to evaluate the predictive value of plasma ACE in radiation pneumonitis (RP). Patients with stage I-III lung cancer were treated with radiotherapy with or without chemotherapy. ACE levels were measured using enzyme-linked immunosorbent assay before radiotherapy (pre-RT) and when a median dose of 45 Gy (Range: 40-48 Gy) was reached (during-RT). The primary end point was > or = grade 2 RP. Statistic significances were evaluated with independent T-test and chi-square. Thirty-nine patients were enrolled in this study, among which 33.3% experienced > or = grade 2 RP. ACE levels, either pre-RT or during-RT, were significantly lower in the RP group than in the non-RP group (P=0.02 and 0.03, respectively). Nine out of the 19 patients (47.4%) with pre-RT ACE levels < or = 462 ng/mL experienced RP, versus 3 of 19 (15.8%) patients with ACE levels > 462 ng/mL (P=0.04). This study suggested that plasma ACE as a predictive factor for radiation pneumonitis deserves further study.     

Electrochemical measurement of hydrogen peroxide in plasma: evaluation of freshwater prawn (Macrobrachium rosenbergii) and crucian carp (Cyprinus carpio) phagocytes under natural conditions

An electrochemical technique for the real-time detection of hydrogen peroxide (H2O2) was employed to describe respiratory burst activity (RBA) of phagocytes in plasma which can be used to evaluate the ability of immune system and disease resistance. The method is based upon the electric current changes, by redox reaction on platinum electrode of extracellular hydrogen peroxide (H2O2) released from phagocytes stimulated by the zymosan at 680 mV direct current (d.c.). Compared with the control, activation of respiratory burst by zymosan particles results in a high amperometric response, and a current peak was obtained during the whole monitoring process. The peak current was proved by addition of Cu2+ and other controls, to be the result of intense release of H2O2 from phagocytes. The peak area was calculated and used to evaluate the quantity of effective H2O2, which represents the quantity of H2O2 beyond the clearance of related enzymes in plasma. According to Faraday's law, the phagocytes' ability of prawns to generate effective H2O2 was evaluated from 1.253 x 10(-14) mol/cell to 6.146 x 10(-14) mol/cell, and carp from 1.689 x 10(-15) mol/cell to 7.873 x 10(-15) mol/cell. This method is an acute and quick detection of extracellular effective H2O2 in plasma and reflects the capacity of phagocytes under natural conditions, which could be applied for selecting species and parents with high immunity for breeding in aquaculture.     

Amplification of apoptosis through sequential caspase cleavage of the MET tyrosine kinase receptor

Activation of the MET tyrosine kinase receptor by hepatocyte growth factor/scatter factor is classically associated with cell survival. Nonetheless, stress stimuli can lead to a caspase-dependent cleavage of MET within its juxtamembrane region, which generate a proapoptotic 40 kDa fragment (p40 MET). We report here that p40 MET is in fact generated through an additional caspase cleavage of MET within its extreme C-terminal region, which removes only few amino acids. We evidenced a hierarchical organization of these cleavages, with the C-terminal cleavage favoring the juxtamembrane one. As a functional consequence, the removal of the last amino acids of p40 MET increases its apoptotic capacity. Finally, cells expressing a MET receptor mutated at the C-terminal caspase site are unable to generate p40 MET and are resistant to apoptosis, indicating that generation of p40 MET amplifies apoptosis. These results revealed a two-step caspase cleavage of MET resulting in the reshaping of this survival receptor to a proapoptotic factor.     

DITOP: drug-induced toxicity related protein database

MOTIVATION: Drug-induced toxicity related proteins (DITRPs) are proteins that mediate adverse drug reactions (ADRs) or toxicities through their binding to drugs or reactive metabolites. Collection of these proteins facilitates better understanding of the molecular mechanisms of drug-induced toxicity and the rational drug discovery. Drug-induced toxicity related protein database (DITOP) is such a database that is intending to provide comprehensive information of DITRPs. Currently, DITOP contains 1501 records, covering 618 distinct literature-reported DITRPs, 529 drugs/ligands and 418 distinct toxicity terms. These proteins were confirmed experimentally to interact with drugs or their reactive metabolites, thus directly or indirectly cause adverse effects or toxicities. Five major types of drug-induced toxicities or ADRs are included in DITOP, which are the idiosyncratic adverse drug reactions, the dose-dependent toxicities, the drug-drug interactions, the immune-mediated adverse drug effects (IMADEs) and the toxicities caused by genetic susceptibility. Molecular mechanisms underlying the toxicity and cross-links to related resources are also provided while available. Moreover, a series of user-friendly interfaces were designed for flexible retrieval of DITRPs-related information. The DITOP can be accessed freely at http://bioinf.xmu.edu.cn/databases/ADR/index.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.     

Extracting three-way gene interactions from microarray data

MOTIVATION: It is an important and difficult task to extract gene network information from high-throughput genomic data. A common approach is to cluster genes using pairwise correlation as a distance metric. However, pairwise correlation is clearly too simplistic to describe the complex relationships among real genes since co-expression relationships are often restricted to a specific set of biological conditions/processes. In this study, we described a three-way gene interaction model that captures the dynamic nature of co-expression relationship between a gene pair through the introduction of a controller gene. RESULTS: We surveyed 0.4 billion possible three-way interactions among 1000 genes in a microarray dataset containing 678 human cancer samples. To test the reproducibility and statistical significance of our results, we randomly split the samples into a training set and a testing set. We found that the gene triplets with the strongest interactions (i.e. with the smallest P-values from appropriate statistical tests) in the training set also had the strongest interactions in the testing set. A distinctive pattern of three-way interaction emerged from these gene triplets: depending on the third gene being expressed or not, the remaining two genes can be either co-expressed or mutually exclusive (i.e. expression of either one of them would repress the other). Such three-way interactions can exist without apparent pairwise correlations. The identified three-way interactions may constitute candidates for further experimentation using techniques such as RNA interference, so that novel gene network or pathways could be identified.     

Mutation of rpoS enhances Pseudomonas sp. KL28 growth at higher concentrations of m-cresol and changes its surface-related phenotypes

A Tn5 transposon mutant was isolated of the alkylphenol degrader Pseudomonas sp. KL28 that showed increased growth at higher levels of m-cresol on solid and in liquid cultures. The transposon was inserted at the 5'-terminus of rpoS, which encodes a stationary-phase sigma factor. When grown on agar plates, the rpoS mutant developed prominent wrinkles, especially at lower temperatures, and spread faster on soft agar. In addition, the rpoS mutant had enhanced biofilm-forming ability that was not due to self-produced diffusible signals.     

Identification of Tannerella forsythia antigens specifically expressed in patients with periodontal disease

Molecular pathogenesis of Tannerella forsythia, a putative periodontal pathogen, has not yet been adequately elucidated due to limited information on its virulence factors. Here, identification of in vivo expressed antigens of T. forsythia is reported using in vivo-induced antigen technology (IVIAT). Among 13 000 recombinant clones screened, 16 positive clones were identified that reacted reproducibly with sera obtained from patients with periodontal disease. DNA sequences from 12 of these in vivo-induced genes were determined. IVIAT-identified protein antigens of T. forsythia include: BspA, a well-defined virulence factor of T. forsythia; enzymes involved in housekeeping functions (tRNA synthetases, glycine hydroxymethyltransferase, and glucoside glucohydrolase); enzymes implicated in tissue destruction (dipeptidyl peptidase IV); a DNA mismatch repair protein; and putative outer membrane proteins of unknown function. The in vivo gene expression of these IVIAT-identified antigens was confirmed by a quantitative real-time PCR analysis. This is, to the best of the authors' knowledge, the first report using IVIAT in T. forsythia. It is anticipated that detailed analysis of the in vivo-induced genes identified by IVIAT in this study will lead to a better understanding of the molecular mechanisms mediating periodontal infection by T. forsythia.     

Protein architecture chronology deduced from structures of amino acid synthases

Inferring the protein architecture chronology is one of central topics in origin of life study and has been given much attention. Based on an amino acid evolutionary model that late amino acids were bio-synthesized prior to early counterparts, we addressed the issue by examining the structures of amino acid synthases. Despite the limited structural information on amino acid synthases, our deduction revealed that alpha/beta was the oldest protein class, which is in good agreement with the prior fold-usage-based conclusion.