Cancer genes hypermethylated in human embryonic stem cells

Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs) in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation.     

Influences of temperature and threshold effect of NaCl concentration on Alpias vulpinus OCT

Thermodynamic, circular dichroism (CD), and activity measurements have been used to characterize the different conformational states and the effects of NaCl concentrations (0.0-3.0 M) on thermal unfolding of ornithine carbamoyltransferase (OCT) from Alopias vulpinus. Furthermore conformational changes in whole enzyme structure have been monitored by titration of SH-groups. OCT unfolding process follows an irreversible two-state mechanism with a first-order kinetic of denaturation, without breaking-point. NaCl shows very little stabilization effects at low concentration and its action become very important over 1.5 M concentration. The presence of 3.0 M NaCl completely avoids OCT unfolding at 60, 64 and 66 degrees C. Kinetic and thermodynamic parameters are strongly influenced by the presence of high NaCl concentration. Our experiments showed that NaCl stabilization process involved changes in preferential binding, in electrostatic and van der Waals interactions and exposure of buried site and SH-groups. During thermal denaturation, UV-vis and CD spectroscopy show that high salts concentration preserves OCT activity, avoiding exposure of hydrophobic site and destruction of secondary and tertiary structure elements.     

Assessing the effect of solar radiation on plant salt tolerance as defined by the static and dynamic indices

Any interaction between plant salt tolerance and environment is critical to crop breeders, geneticists, molecular biologists, soil-water-crop modelers and all researchers interested in 'global change'. A common criterion used for plant salt tolerance is a threshold value of root zone salinity, a static index that delimits the onset of yield reduction. According to this criterion, it was discovered that tomato salt tolerance decreases significantly with reduced solar radiation. In contrast, the threshold values of a new index based on the dynamic processes of salt accumulation relative to growth, are invariant to solar radiation. The variability and stability of the respective indices provides new insights for accessing physical and biochemical processes governing plant response in saline environments.     

Structural characteristics and plant-beneficial effects of bacteria colonizing the shoots of field grown conventional and genetically modified T4-lysozyme producing potatoes

Genetically modified potatoes expressing antibacterial protein T4 lysozyme may offer effective control strategies for bacterial pathogens causing severe potato diseases. Apart from this beneficial effect, it is very important to investigate such engineered potatoes carefully for potential adverse effects on potato-associated bacteria which frequently exhibit plant beneficial functions such as plant growth promotion and antagonism towards pathogens invading the plant. Two field experiments were carried out in Spain to analyze the potential effects of conventional and genetically modified T4-lysozyme producing potatoes on shoot-associated bacteria. The first baseline field trial 2002 was performed in Meliana in which three conventional potato lines, Achirana Inta, Desirée, and Merkur, were cultivated and sampled at flowering. The second field trial was conducted in Cella in 2003 in order to compare the effects of a senescent transgenic, T4 lysozyme expressing potato trait, Desirée DL 12, with its isogenic, non-transformed parental line Desirée. Structural characteristics of potato shoot-associated bacteria was assayed by 16S rRNA-based terminal restriction fragment length polymorphism (T-RFLP) analysis and dominant community members within T-RFLP profiles were identified by sequence analysis of generated 16S rRNA gene libraries. Cultivable bacteria isolated from shoots of potatoes grown in the Meliana field trial were monitored for antibiosis against Ralstonia solanacearum, whereas isolates derived from shoots of potatoes cultivated in the Cella trial were screened for antagonism against Ralstonia solanacearum and Rhizoctonia solani, and for 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase production. Determined antagonists were identified by 16S rRNA gene analysis. All potato traits hosted a cultivar-specific community of bacteria with antagonism against the pathogens and/or potential to produce ACC deaminase. Several antagonists obtained from the Cella field potatoes were also observed as ACC deaminase producers. Community profiling revealed a greater diversity differentiation between the senescent T4 lysozyme expressing and parental Desirée lines grown in the Cella field as compared to the variations between the three flowering conventional lines cultivated in the Meliana field trial. Effects of the two varying field sites and different vegetation stages were greater than those of T4 lysozyme when investigating the community composition of bacteria colonizing the shoots of the Desirée line cultivated in both field trials.     

Chiari Malformation Type I: A Case-Control Association Study of 58 Developmental Genes

Chiari malformation type I (CMI) is a disorder characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa (PCF), often causing progressive neurological symptoms. The etiology of CMI remains unclear and is most likely multifactorial. A putative genetic contribution to CMI is suggested by familial aggregation and twin studies. Experimental models and human morphometric studies have suggested an underlying paraxial mesoderm insufficiency. We performed a case-control association study of 303 tag single nucleotide polymorphisms (SNP) across 58 candidate genes involved in early paraxial mesoderm development in a sample of 415 CMI patients and 524 sex-matched controls. A subgroup of patients diagnosed with classical, small-PCF CMI by means of MRI-based PCF morphometry (n = 186), underwent additional analysis. The genes selected are involved in signalling gradients occurring during segmental patterning of the occipital somites (FGF8, Wnt, and retinoic acid pathways and from bone morphogenetic proteins or BMP, Notch, Cdx and Hox pathways) or in placental angiogenesis, sclerotome development or CMI-associated syndromes. Single-marker analysis identified nominal associations with 18 SNPs in 14 genes (CDX1, FLT1, RARG, NKD2, MSGN1, RBPJ1, FGFR1, RDH10, NOG, RARA, LFNG, KDR, ALDH1A2, BMPR1A) considering the whole CMI sample. None of these overcame corrections for multiple comparisons, in contrast with four SNPs in CDX1, FLT1 and ALDH1A2 in the classical CMI group. Multiple marker analysis identified a risk haplotype for classical CMI in ALDH1A2 and CDX1. Furthermore, we analyzed the possible contributions of the most significantly associated SNPs to different PCF morphometric traits. These findings suggest that common variants in genes involved in somitogenesis and fetal vascular development may confer susceptibility to CMI.     

Profiling of Volatile Organic Compounds in Exhaled Breath As a Strategy to Find Early Predictive Signatures of Asthma in Children

Wheezing is one of the most common respiratory symptoms in preschool children under six years old. Currently, no tests are available that predict at early stage who will develop asthma and who will be a transient wheezer. Diagnostic tests of asthma are reliable in adults but the same tests are difficult to use in children, because they are invasive and require active cooperation of the patient. A non-invasive alternative is needed for children. Volatile Organic Compounds (VOCs) excreted in breath could yield such non-invasive and patient-friendly diagnostic. The aim of this study was to identify VOCs in the breath of preschool children (inclusion at age 2–4 years) that indicate preclinical asthma. For that purpose we analyzed the total array of exhaled VOCs with Gas Chromatography time of flight Mass Spectrometry of 252 children between 2 and 6 years of age. Breath samples were collected at multiple time points of each child. Each breath-o-gram contained between 300 and 500 VOCs; in total 3256 different compounds were identified across all samples. Using two multivariate methods, Random Forests and dissimilarity Partial Least Squares Discriminant Analysis, we were able to select a set of 17 VOCs which discriminated preschool asthmatic children from transient wheezing children. The correct prediction rate was equal to 80% in an independent test set. These VOCs are related to oxidative stress caused by inflammation in the lungs and consequently lipid peroxidation. In conclusion, we showed that VOCs in the exhaled breath predict the subsequent development of asthma which might guide early treatment.     

Looking beyond the post-genomic era

A report on BioMed Central’s fourth annual Beyond the Genome conference held at the University of California, San Francisco Mission Bay Conference Center, USA, 1–3 October 2013.     

EcXyl43 β-xylosidase: molecular modeling,activity on natural and artificial substrates,and synergism with endoxylanases for lignocellulose deconstruction

Applied Microbiology and Biotechnology - Biomass hydrolysis constitutes a bottleneck for the biotransformation of lignocellulosic residues into bioethanol and high-value products. The efficient...