Silicon increases phosphorus (P) uptake by wheat under low P acid soil conditions

Plant and Soil - Although silicon (Si) is known to improve plant growth under low phosphorus (P) conditions, the in planta mechanisms responsible for this effect are still unknown. Here, we...     

The CFTR M470V gene variant as a potential modifier of COPD severity: study of Serbian population

Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by genetic and environmental factors. Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an important component of the lung tissue homeostasis, involved in the regulation of the rate of mucociliary clearance. As it is known that certain CFTR variants have consequences on the function of CFTR protein, the aim of this study was to examine the possible role of F508del, M470V, Tn locus, and R75Q variants in COPD development and modulation. Total number of 86 COPD patients and 102 control subjects were included in the study. Possible association between COPD susceptibility, severity, and onset of the disease and allele or genotype of four analyzed CFTR variants was examined. No associations were detected between COPD development, onset of the disease and tested CFTR alleles and genotypes. However, VV470 genotype was associated with mild/moderate COPD stages in comparison to severe/very severe ones (OR = 0.29, 95%CI = 0.11-0.80, p = 0.016). Our study showed that patients with VV470 genotype had a 3.4-fold decreased risk for the appearance of severe/very severe COPD symptoms, and the obtained results indicate that this genotype may have a protective role. These results also suggest the importance of studying CFTR gene as a modifier of this disease.     

Tandem immunoprecipitation of phosphotyrosine-mass spectrometry (TIPY-MS) indicates C19ORF19 becomes tyrosine-phosphorylated and associated with activated epidermal growth factor receptor

To identify phosphotyrosine (pY) sites in the epidermal growth factor receptor (EGFR) network, a tandem immunoprecipitation-mass spectrometry method (TIPY-MS) was applied wherein protease-digested EGFR immune complexes were extracted with anti-pY after Rush et al. ( Nat. Biotech. 2005, 23, 94 ) and analyzed by LC-MS/MS. New pY sites in the pathway were found, including SOS1 Y1065, SOS2 Y1275, CBL-B Y889, and in the EGFR regulatory protein Mig-6 Y458. The novel human C19orf19 gene product was found EGFR-associated and phosphorylated at 5 tyrosines in response to EGFR activation and, therefore, represents a new component of the EGFR signaling network.     

GABAergic phthalide dimers from Angelica sinensis (Oliv.) Diels

The methanol extract of Angelica sinensis (Oliv.) Diels roots (Dang Gui) has been shown to exhibit competitive binding to the GABAa receptor, suggesting the presence of GABAergic ligands. Chromatographic fractionation of the methanol extract led to the isolation of two GABAergic dimeric phthalides 1 and 2. Gelispirolide (1) was elucidated as a new phthalide dimer composed of a Z-ligustilide and a Z-butylidenephthalide unit on the basis of spectroscopic approaches including one- and two-dimensional NMR, HRESIMS and HRESIMS-MS. Compound 2 was identified as the known dimeric phthalide, riligustilide, by comparison of its spectroscopic data with literature values. Its dimeric linkage and stereochemistry were ascertained by a single crystal X-ray diffraction experiment. Both dimers 1 and 2 were found to be active in an in vitro GABAa receptor-binding assay with IC50 values of 29 and 24 microM, respectively.     

Regulation of the mutually exclusive exons 8a and 8 in the CaV1.2 calcium channel transcript by polypyrimidine tract-binding protein

CaV1.2 calcium channels play roles in diverse cellular processes such as gene regulation, muscle contraction, and membrane excitation and are diversified in their activity through extensive alternative splicing of the CaV1.2 mRNA. The mutually exclusive exons 8a and 8 encode alternate forms of transmembrane segment 6 (IS6) in channel domain 1. The human genetic disorder Timothy syndrome is caused by mutations in either of these two CaV1.2 exons, resulting in disrupted Ca(2+) homeostasis and severe pleiotropic disease phenotypes. The tissue-specific pattern of exon 8/8a splicing leads to differences in symptoms between patients with exon 8 or 8a mutations. Elucidating the mechanisms controlling the exon 8/8a splicing choice will be important in understanding the spectrum of defects associated with the disease. We found that the polypyrimidine tract-binding protein (PTB) mediates a switch from exon 8 to 8a splicing. PTB and its neuronal homolog, nPTB, are widely studied splicing regulators controlling large sets of alternative exons. During neuronal development, PTB expression is down-regulated with a concurrent increase in nPTB expression. Exon 8a is largely repressed in embryonic mouse brain but is progressively induced during neuronal differentiation as PTB is depleted. This splicing repression is mediated by the direct binding of PTB to sequence elements upstream of exon 8a. The nPTB protein is a weaker repressor of exon 8a, resulting in a shift in exon choice when nPTB replaces PTB in cells. These results provide mechanistic understanding of how these two exons, important for human disease, are controlled.