Using co-occurrence network structure to extract synonymous gene and protein names from MEDLINE abstracts

Background  

Text-mining can assist biomedical researchers in reducing information overload by extracting useful knowledge from large collections of text. We developed a novel text-mining method based on analyzing the network structure created by symbol co-occurrences as a way to extend the capabilities of knowledge extraction. The method was applied to the task of automatic gene and protein name synonym extraction.     

Iron, Nitric Oxide, and Myeloperoxidase in Asthmatic Patients

Plasma nitric oxide (NO), myeloperoxidase (MPO), and iron (Fe) levels were determined in bronchial asthma. The relations among these parameters in different stages of asthma were interpreted. Their association with airway inflammation observed in patients with bronchial asthma as well as the roles and the contributions to the pathological processes were evaluated. A total of 62 individuals, 32 asthmatics and 30 controls, were included into the scope of this study. Plasma nitric oxide metabolites (NOx) and MPO and Fe levels were determined by the Griess reaction, ELISA, and the automated TPTZ (2,4,6-tri[2-pyridyl]-5-triazine) method, respectively. In the asthmatic individuals, plasma NOx, MPO, and Fe concentrations were 133 +/- 13 microM, 95 +/- 20 ng/ml, and 159 +/- 20 microg/dl, respectively; in the control group these values were 82 +/- 11 microM, 62 +/- 11 ng/ml, and 96 +/- 9 microg/dl. Increased values were detected for plasma MPO (p > 0.05), NOx (p < 0.01), and Fe (p < 0.01) concentrations in asthmatic individuals. Considering the facts that NO modulates the catalytic activity of MPO and induces the expression of heme oxygenase as important contributors to the mechanisms causing free Fe release, it is concluded that elevated NOx, MPO, and Fe levels observed in the asthmatic group act in a concerted manner and appear to be involved in the pathogenesis of asthma.     

Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. We first identified a PAM locus by homozygosity mapping to 4p15, then identified, by a candidate-gene approach, the gene responsible for the disease as SLC34A2 (the type IIb sodium-phosphate cotransporter gene), which is involved in phosphate homeostasis in several organs. We identified six homozygous exonic mutations in the seven unrelated patients with PAM we studied. Three of the mutations were frameshifts, one was a chain termination, one was an amino acid substitution, and one was a deletion spanning the minimal promoter and the first exon. Absence of functional protein product of the gene is compatible with calcium phosphate deposition in alveolar airspaces. We show that impaired activity of the phosphate transporter is presumably responsible for the microliths and that PAM is a recessive monogenic disease with full penetrance. Testicular microlithiasis (TM) is a disease that is more common than PAM. It is often associated with cancer and infertility. Since the gene we identified is also expressed in testis, we searched for mutations in subjects with TM. In 2 of the 15 subjects with TM we studied, we identified two rare variants, one synonymous and the other noncoding, that are possibly associated with the condition.     

Ubiquitin crosstalk connecting cellular processes

Cullin 4 (Cul4), a member of the evolutionally conserved cullin protein family, serves as a scaffold to assemble multisubunit ubiquitin E3 ligase complexes. Cul4 interacts with the Ring finger-containing protein ROC1 through its C-terminal cullin domain and with substrate recruiting subunit(s) through its N-terminus. Previous studies have demonstrated that Cul4 E3 ligase ubiquitylates key regulators in cell cycle control and mediates their degradation through the proteasomal pathway, thus contributing to genome stability. Recent studies from several groups have revealed that Cul4 E3 ligase can target histones for ubiquitylation, and importantly, ubiquitylation of histones may facilitate the cellular response to DNA damage. Therefore, histone ubiquitylation by Cul4 E3 ligase constitutes a novel mechanism through which Cul4 regulates chromatin function and maintains genomic integrity. We outline these studies and suggest that histone ubiquitylation might play important roles in Cul4-regualted chromatin function including the cellular response to DNA damage and heterochromatin gene silencing.     

Tyrosine-specific MAPK phosphatases and the control of ERK signaling in PC12 cells

Background

Spatio-temporal control of extracellular signal-regulated kinase (ERK) activity, a critical determinant of the cell's response to growth factors, requires timely dephosphorylation of its regulatory tyrosine and/or threonine residue by MAPK phosphatases. We studied the physiological role of kinase interaction motif (KIM)-containing protein tyrosine phosphatases (PTPs) in the control of EGF- and NGF-induced ERK activity in neuroendocrine PC12 cells.

Results

We found a single KIM-containing PTP to be endogenously expressed in rat PC12 cells: the transmembrane PTPRR isoform termed PCPTP1. Protein knock-down of PCPTP1, or fourfold overexpression of its mouse orthologue, PTPBR7, left EGF- and NGF-induced ERK1/2 activity in PC12 cells unaltered. Ectopic expression of cytosolic PTPRR isoforms, however, resulted in reduced EGF-induced ERK1/2 activity, an effect that was dependent on the phosphatase activity and the KIM-domain of these PTPs.

Conclusion

The finding that robust changes in tyrosine-specific MAPK phosphatase expression levels have minor effects on temporal ERK1/2 activity control in PC12 cells suggests that dual-specificity MAPK phosphatases may act as major regulators of growth factor-induced ERK1/2 signaling in these cells.     

Sensitivity of methods for estimating breeding values using genetic markers to the number of QTL and distribution of QTL variance

The objective of this simulation study was to compare the effect of the number of QTL and distribution of QTL variance on the accuracy of breeding values estimated with genomewide markers (MEBV). Three distinct methods were used to calculate MEBV: a Bayesian Method (BM), Least Angle Regression (LARS) and Partial Least Square Regression (PLSR). The accuracy of MEBV calculated with BM and LARS decreased when the number of simulated QTL increased. The accuracy decreased more when QTL had different variance values than when all QTL had an equal variance. The accuracy of MEBV calculated with PLSR was affected neither by the number of QTL nor by the distribution of QTL variance. Additional simulations and analyses showed that these conclusions were not affected by the number of individuals in the training population, by the number of markers and by the heritability of the trait. Results of this study show that the effect of the number of QTL and distribution of QTL variance on the accuracy of MEBV depends on the method that is used to calculate MEBV.     

The effects of subchronic methidathion toxicity on rat liver: Role of antioxidant vitamins C and E

Methidathion (MD) phosphorodithioic acid S-[(5-methoxy-2-oxo-1,3,4-thiadiazol-3(2H)-yl)methyl] O,O-dimethyl ester is the organophosphate insecticide (OPI) most commonly used worldwide in the pest control of crops. Subchronic MD exposure was evaluated for its effects on lipid peroxidation, the serum activities of cholinesterase (ChE), and enzymes concerning liver damage, and the protective effects of combination of vitamins E and C in albino rats. Additionally, the histopathological changes in liver tissue were examined. Experimental groups were as follows: control group; a group treated with 5 mg/kg body weight MD (MD group); and a group treated with 5 mg/kg body wight MD plus vitamin E plus vitamin C (MD+AO group). The MD and MD+AO groups were treated orally with MD on five days a week for 4 weeks. The serum activities of cholinesterase (ChE), alanine transferase (ALT), aspartate amiotransferase (AST), lactate dehydrogenase (LDH), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), and the concentration of malondialdehyde (MDA) and liver histopathology were studied. In serum samples, MD significantly increased MDA concentration and ALP, AST, GGT, LDH activities but decreased the ALT and ChE activities. In the MD+AO group, MDA level and ALP, AST, LDH activities were significantly decreased and ChE activity was increased compared to the MD group. Histopathological changes found in liver tissue of rats treated with MD included were infiltration with mononuclear cells in all portal areas, sinusoidal dilatation, and focal microvesicular steatosis and hydropic degenerations in parenchymal tissue. The severity of these lesions was reduced by administration of vitamins. From these results, it can be concluded that subchronic MD causes liver damage, and lipid peroxidation may be a molecular mechanism involved in MD-induced toxicity. Furthermore, the combination of vitamins E and C can reduce the toxic effects of MD on liver tissue of rats.     

The Interactions of Nitric Oxide and Acetylcholine on Penicillin-Induced Epilepsy in Rats

The aim of this study was to investigate the interaction between nitric oxide (NO) and acetylcholine (ACh) in penicillin-induced experimental epilepsy. Adult male Wistar rats weighing 220 ± 35 g were used in the experiments. The epileptiform activity was induced by microinjection of penicillin (200 IU/1 μl) into the left sensorymotor cortex. Electrocorticogram was recorded by using Ag/AgCl ball electrodes. Sodium nitroprusside (SNP), a NO donor, given intracortically 30 min after penicillin significantly reduced the spike frequency whereas ACh increased the epileptiform activity for 5 min. Atropine, an antagonist for muscarinic receptors, was given intracortically 30 min after penicillin and did not significantly affect epileptiform activity for 30 min. SNP given after atropine significantly suppressed the epileptiform activity. ACh given 10 min after Nω-nitro-L: -arginine methyl ester (L-NAME), a nonspecific nitric oxide synthase inhibitor, did not have a significant effect on spike frequency. When ACh and SNP were administered together, penicillin induced epileptiform activity and spike frequency were significantly suppressed from the 10th minute onwards. It can be concluded that ACh increases the penicillin-induced epileptiform activity while co-administration of ACh and SNP produces a potent anticonvulsant effect as compared to SNP alone.     

Heavy Metal and Disinfectant Resistance of Listeria monocytogenes from Foods and Food Processing Plants

The persistence of Listeria monocytogenes in food processing plants and other ecosystems reflects its ability to adapt to numerous stresses. In this study, we investigated 138 isolates from foods and food processing plants for resistance to the quaternary ammonium disinfectant benzalkonium chloride (BC) and to heavy metals (cadmium and arsenic). We also determined the prevalence of distinct cadmium resistance determinants (cadA1, cadA2, and cadA3) among cadmium-resistant isolates. Most BC-resistant isolates were resistant to cadmium as well. Arsenic resistance was encountered primarily in serotype 4b and was an attribute of most isolates of the serotype 4b epidemic clonal group ECIa. Prevalence of the known cadmium resistance determinants was serotype associated: cadA1 was more common in isolates of serotypes 1/2a and 1/2b than 4b, while cadA2 was more common in those of serotype 4b. A subset (15/77 [19%]) of the cadmium-resistant isolates lacked the known cadmium resistance determinants. Most of these isolates were of serotype 4b and were also resistant to arsenic, suggesting novel determinants that may confer resistance to both cadmium and arsenic in these serotype 4b strains. The findings may reflect previously unrecognized components of the ecological history of different serotypes and clonal groups of L. monocytogenes, including exposures to heavy metals and disinfectants.     

Refining the roots of the beewolf-Streptomyces symbiosis: antennal symbionts in the rare genus Philanthinus (Hymenoptera, Crabronidae)

Insects engage in symbiotic associations with a large diversity of beneficial microorganisms. While the majority of well-studied symbioses have a nutritional basis, several cases are known in which bacteria protect their host from pathogen infestation. Solitary wasps of the genera Philanthus and Trachypus (beewolves; Hymenoptera, Crabronidae) cultivate the actinomycete "Candidatus Streptomyces philanthi" in specialized antennal gland reservoirs. The symbionts are transferred to the larval cocoon, where they provide protection against pathogenic fungi by producing at least nine different antibiotics. Here we investigated the closest relatives of Philanthus and Trachypus, the rare genus Philanthinus, for the presence of antennal gland reservoirs and symbiotic streptomycetes. Molecular analyses identified "Ca. Streptomyces philanthi" in reservoirs of Philanthinus quattuordecimpunctatus. Phylogenies based on the 16S rRNA gene suggest that P. quattuordecimpunctatus may have acquired "Ca. Streptomyces philanthi" by horizontal transfer from other beewolf species. In histological sections and three-dimensional reconstructions, the antennal gland reservoirs were found to occupy six antennal segments (as opposed to only five in Philanthus and Trachypus) and to be structurally less complex than those of the evolutionarily more derived genera of beewolves. The presence of "Ca. Streptomyces philanthi" in antennal glands of Philanthinus indicates that the symbiosis between beewolves and Streptomyces bacteria is much older than previously thought. It probably evolved along the branch leading to the monophyletic tribe Philanthini, as it seems to be confined to the genera Philanthus, Trachypus, and Philanthinus, which together comprise 172 described species of solitary wasps.