Primary Founder Mutations in the PRKDC Gene Increase Tumor Mutation Load in Colorectal Cancer

The clonal composition of a malignant tumor strongly depends on cellular dynamics influenced by the asynchronized loss of DNA repair mechanisms. Here, our aim was to identify founder mutations leading to subsequent boosts in mutation load. The overall mutation burden in 591 colorectal cancer tumors was analyzed, including the mutation status of DNA-repair genes. The number of mutations was first determined across all patients and the proportion of genes having mutation in each percentile was ranked. Early mutations in DNA repair genes preceding a mutational expansion were designated as founder mutations. Survival analysis for gene expression was performed using microarray data with available relapse-free survival. Of the 180 genes involved in DNA repair, the top five founder mutations were in PRKDC (n = 31), ATM (n = 26), POLE (n = 18), SRCAP (n = 18), and BRCA2 (n = 15). PRKDC expression was 6.4-fold higher in tumors compared to normal samples, and higher expression led to longer relapse-free survival in 1211 patients (HR = 0.72, p = 4.4 × 10⁻³). In an experimental setting, the mutational load resulting from UV radiation combined with inhibition of PRKDC was analyzed. Upon treatments, the mutational load exposed a significant two-fold increase. Our results suggest PRKDC as a new key gene driving tumor heterogeneity.     

Processing of preconsciously acquired information measured by hemispheric asymmetry and selection accuracy.

Two groups of 14 right-handed female undergraduates saw a series of slides for 1 msec. Subsequently, these slides were paired with similar but novel slides. One group was asked to view the pairs analytically and to select the one they thought they had seen before. The other group was asked to view the pairs holistically and indicate which of the 2 they preferred. Results support the hypothesis that analytically instructed Ss would be more likley to engage the parietal region of their left hemisphere and holistically instructed Ss would favor relative activation of the right parietal region. An inverse relation was also detected between parietal laterality and selection accuracy. It is suggested that differential hemispheric involvement may account for the observation that affective discrimination can be performed in the absence of conscious awareness. Findings are discussed in terms of a memory model of information processing. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microstructural Features Leading to Enhanced Resistance to Grain Boundary Creep Cracking in ALLVAC 718Plus

This study focuses on the microstructural features that enhance the resistance of ALLVAC 718Plus to grain boundary creep cracking during testing of samples at 704 °C in both dry and moist air. Fully recrystallized structures were found to be susceptible to brittle grain boundary cracking in both environments. Detailed transmission electron microscopy (TEM) microstructural characterization reveals features that are believed to lead to resistance to grain boundary cracking in the resistant microstructures. It is suggested that dislocation substructures found within the grains of resistant structures compete with the high-angle grain boundaries for oxygen, thereby reducing the concentration of oxygen on the grain boundaries and subsequent embrittlement. In addition, electron backscatter diffraction (EBSD) misorientation maps reveal that special boundaries (i.e., Σ3 boundaries) resist cracking. This is in agreement with previous findings on the superalloy INCONEL 718. Furthermore, it is observed that cracks propagate along high-angle boundaries. This study also shows that in this case, the presence of delta phase at the grain boundaries does not by itself produce materials that are resistant to grain boundary cracking.     

Glutathione Deficiency during Early Postnatal Development Causes Schizophrenia-Like Symptoms and a Reduction in BDNF Levels in the Cortex and Hippocampus of Adult Sprague–Dawley Rats

Growing body of evidence points to dysregulation of redox status in the brain as an important factor in the pathogenesis of schizophrenia. The aim of our study was to evaluate the effects of l-buthionine-(S,R)-sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, and 1-[2-Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12909), a dopamine reuptake inhibitor, given alone or in combination, to Sprague–Dawley pups during early postnatal development (p5–p16), on the time course of the onset of schizophrenia-like behaviors, and on the expression of brain-derived neurotrophic factor (BDNF) mRNA and its protein in the prefrontal cortex (PFC) and hippocampus (HIP) during adulthood. BSO administered alone decreased the levels of BDNF mRNA and its protein both in the PFC and HIP. Treatment with the combination of BSO + GBR 12909 also decreased BDNF mRNA and its protein in the PFC, but in the HIP, only the level of BDNF protein was decreased. Schizophrenia-like behaviors in rats were assessed at three time points of adolescence (p30, p42–p44, p60–p62) and in early adulthood (p90–p92) using the social interaction test, novel object recognition test, and open field test. Social and cognitive deficits first appeared in the middle adolescence stage and continued to occur into adulthood, both in rats treated with BSO alone or with the BSO + GBR 12909 combination. Behavior corresponding to positive symptoms in humans occurred in the middle adolescence period, only in rats treated with BSO + GBR 12909. Only in the latter group, amphetamine exacerbated the existing positive symptoms in adulthood. Our data show that rats receiving the BSO + GBR 12909 combination in the early postnatal life reproduced virtually all symptoms observed in patients with schizophrenia and, therefore, can be considered a valuable neurodevelopmental model of this disease.     

Genetic Carriers and Genomic Distribution of cadA6—A Novel Variant of a Cadmium Resistance Determinant Identified in Listeria spp.

Listeria monocytogenes is a pathogen responsible for severe cases of food poisoning. Listeria spp. strains occurring in soil and water environments may serve as a reservoir of resistance determinants for pathogenic L. monocytogenes strains. A large collection of Listeria spp. strains (155) isolated from natural, agricultural, and urban areas was screened for resistance to heavy metals and metalloids, and the presence of resistance determinants and extrachromosomal replicons. Of the tested strains, 35% were resistant to cadmium and 17% to arsenic. Sequence analysis of resistance plasmids isolated from strains of Listeria seeligeri and Listeria ivanovii, and the chromosome of L. seeligeri strain Sr73, identified a novel variant of the cadAC cadmium resistance efflux system, cadA6, that was functional in L. monocytogenes cells. The cadA6 cassette was detected in four Listeria species, including strains of L. monocytogenes, isolated from various countries and sources—environmental, food-associated, and clinical samples. This resistance cassette is harbored by four novel composite or non-composite transposons, which increases its potential for horizontal transmission. Since some cadAC cassettes may influence virulence and biofilm formation, it is important to monitor their presence in Listeria spp. strains inhabiting different environments.     

Monitoring biodegradation of ethene and bioremediation of chlorinated ethenes at a contaminated site using compound-specific isotope analysis (CSIA)

Chlorinated ethenes are commonly found in contaminated groundwater. Remediation strategies focus on transformation processes that will ultimately lead to nontoxic products. A major concern with these strategies is the possibility of incomplete dechlorination and accumulation of toxic daughter products (cis-1,2-dichloroethene (cDCE), vinyl chloride (VC)). Ethene mass balance can be used as a direct indicator to assess the effectiveness of dechlorination. However, the microbial processes that affect ethene are not well characterized and poor mass balance may reflect biotransformation of ethene rather than incomplete dechlorination. Microbial degradation of ethene is commonly observed in aerobic systems but fewer cases have been reported in anaerobic systems. Limited information is available on the isotope enrichment factors associated with these processes. Using compound-specific isotope analysis (CSIA) we determined the enrichment factors associated with microbial degradation of ethene in anaerobic microcosms (ε = -6.7‰ ± 0.4‰, and -4.0‰ ± 0.8‰) from cultures collected from the Twin Lakes wetland area at the Savannah River site in Georgia (United States), and in aerobic microcosms (ε = -3.0‰ ± 0.3‰) from Mycobacterium sp. strain JS60. Under anaerobic and aerobic conditions, CSIA can be used to determine whether biotransformation of ethene is occurring in addition to biodegradation of the chlorinated ethenes. Using δ(13)C values determined for ethene and for chlorinated ethenes at a contaminated field site undergoing bioremediation, this study demonstrates how CSIA of ethene can be used to reduce uncertainty and risk at a site by distinguishing between actual mass balance deficits during reductive dechlorination and apparent lack of mass balance that is related to biotransformation of ethene.     

Mechanical Effects in Saturated Capillary-Porous Materials during Convective and Microwave Drying

The differences are analyzed in distribution and time evolution of the temperature, moisture content, and drying-induced stresses generated by convective and microwave drying. The theoretical analysis of the drying induced stresses and the deformations of dried materials is based on the elastic and viscoelastic constitutive models. The theoretical predictions are confronted with the experimental data obtained by the acoustic emission (AE) method, which enable monitoring on line the development of the drying induced stresses. The system of double coupled differential equations of the thermomechanical drying model is solved numerically using the finite element (FEM) and the finite difference (FDM) methods. A cylindrical sample made of kaolin was chosen to compare experimental data with the model solution. Essential differences were identified in the analyzed items for convective and microwave drying as well as a significant difference in stress distribution was noted for elastic and viscoelastic constitutive models.     

Silicon compounds as additives improving coating performance: fixation of silicon compounds with cellulose

In this study the reactivity of cellulose with new solvent born preparations containing organosilanes, alkyd resin and natural oil was analysed. Structural analysis of cellulose after reaction with organosilanes and after extraction was performed using Fourier-transform infrared spectroscopy (FTIR). In IR spectra the analyzed bands included 1250 cm⁻¹ responsible for vibrations of the SiC group and 800 cm⁻¹ responsible for vibrations of SiC and/or SiO groups. These bands are characteristic of silicon bonds with atoms of carbon and oxygen originating from the methoxy groups found in organosilanes. The presence of these bands in the spectra proves the occurrence of a reaction between cellulose and organosilanes. The concentration of silicon was determined by AAS in cellulose after reaction with preparations and after extraction.