Evidence of altered histone interactions, as investigated by removal of histones, in chromatin isolated from rat liver nuclei by a conventional method.

It is shown that the release of the slightly lysine-rich histones f2a2 and f2b by 0.4 M ammonium sulfate from conventionally isolated chromatin is diminished in comparison to the lysed nuclei. The change in extractability is further demonstrated by the application of ethidium bromide. At a molar input ratio of 0.09 (moles ethidium bromide/moles nucleotide) and 0.4 M ammonium sulfate the slightly lysine-rich histones are released from the chromatin to 70 - 80% if the lysed nuclei are used. At 0.1 M ammonium sulfate ethidium bromide effected also a release of 50 % of histone f1. Comparable effects could not be observed with chromatin prepared in a conventional way but instead a tendency towards loss of histone f3 in the presence of ethidium bromide was observed.     

Novel inhibitors of epidermal growth factor receptor: (4-(Arylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)(1H-indol-2-yl)methanones and (1H-indol-2-yl)(4-(phenylamino)thieno[2,3-d]pyrimidin-6-yl)methanones

Several members of the quinazoline class of known tyrosine kinase inhibitors are approved anticancer agents, often showing selectivity for receptors of the HER/ErbB-family. Combining structural elements of this class with the bisindolylmethanone-structure led to a series of novel compounds. These compounds inhibited EGFR in the nanomolar range. Moreover, inhibition of EGFR autophosphorylation in intact A431 cells was shown, with IC₅₀ values ranging form 0.3–1 μM for compound 42, and 0.1–0.3 μM for 45. In a panel of 42 human tumor cell lines the sensitivity profile of the novel compounds was shown to be similar to that of the quinazoline class of tyrosine kinase inhibitors lapatinib and erlotinib (Tarceva®).     

Troponin and Anti-Troponin Autoantibody Levels in Patients with Ventricular Noncompaction

Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24) and noncompaction with reduced EF (LVEF <35%, n = 26) groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group), troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group) and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group) levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG). Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients.     

Maintenance of low histone ubiquitylation by Ubp10 correlates with telomere-proximal Sir2 association and gene silencing

Low levels of histone covalent modifications are associated with gene silencing at telomeres and other regions in the yeast S. cerevisiae. Although the histone deacetylase Sir2 maintains low acetylation, mechanisms responsible for low H2B ubiquitylation and low H3 methylation are unknown. Here, we show that the ubiquitin protease Ubp10 targets H2B for deubiquitylation, helping to localize Sir2 to the telomere. Ubp10 exhibits reciprocal Sir2-dependent preferential localization proximal to telomeres, where Ubp10 serves to maintain low H2B Lys123 ubiquitylation in this region and, through previously characterized crosstalk, maintains low H3 Lys4 and Lys79 methylation in a slightly broader region. Ubp10 is also localized to the rDNA locus, a second silenced domain, where it similarly maintains low histone methylation. We compare Ubp10 to Ubp8, the SAGA-associated H2B deubiquitylase involved in gene activation, and show that telomeric and gene-silencing functions are specific to Ubp10. Our results suggest that these H2B-deubiquitylating enzymes have distinct genomic functions.     

Decision tree based information integration for automated protein classification

We propose a novel technique for automatically generating the SCOP classification of a protein structure with high accuracy. We achieve accurate classification by combining the decisions of multiple methods using the consensus of a committee (or an ensemble) classifier. Our technique, based on decision trees, is rooted in machine learning which shows that by judicially employing component classifiers, an ensemble classifier can be constructed to outperform its components. We use two sequence- and three structure-comparison tools as component classifiers. Given a protein structure and using the joint hypothesis, we first determine if the protein belongs to an existing category (family, superfamily, fold) in the SCOP hierarchy. For the proteins that are predicted as members of the existing categories, we compute their family-, superfamily-, and fold-level classifications using the consensus classifier. We show that we can significantly improve the classification accuracy compared to the individual component classifiers. In particular, we achieve error rates that are 3-12 times less than the individual classifiers' error rates at the family level, 1.5-4.5 times less at the superfamily level, and 1.1-2.4 times less at the fold level.     

Arctic Geese Tune Migration to a Warming Climate but Still Suffer from a Phenological Mismatch

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Plant pressure sensitive adhesives: similar chemical properties in distantly related plant lineages

Main conclusion

A mixture of resins based on aliphatic esters and carboxylic acids occurs in distantly related genera Peperomia and Roridula , serving different functions as adhesion in seed dispersal and prey capture. According to mechanical characteristics, adhesive secretions on both leaves of the carnivorous flypaper Roridula gorgonias and epizoochorous fruits of Peperomia polystachya were expected to be similar. The chemical analysis of these adhesives turned out to be challenging because of the limited available mass for analysis. Size exclusion chromatography and Fourier transform infrared spectroscopy were suitable methods for the identification of a mixture of compounds, most appropriately containing natural resins based on aliphatic esters and carboxylic acids. The IR spectra of the Peperomia and Roridula adhesive resemble each other; they correspond to that of a synthetic ethylene–vinyl acetate copolymer, but slightly differ from that of natural tree resins. Thus, the pressure sensitive adhesive properties of the plant adhesives are chemically proved. Such adhesives seem to appear independently in distantly related plant lineages, habitats, life forms, as well as plant organs, and serve different functions such as prey capture in Roridula and fruit dispersal in Peperomia. However, more detailed chemical analyses still remain challenging because of the small available volume of plant adhesive.

     

Metal-induced sequential transitions among DNA conformations

The action of [Co(NH₃)₆]Cl₃ on poly(dGdC) · poly(dGdC) can lead to a series of consecutive reactions, in which B-DNA is first converted to Z-DNA [M. Behe and G. Felsenfeld (1981) Proc. Natl. Acad. Sci USA 78 , 1619–1623], which in turn is transformed into an unidentified conformer that we tentatively call “U”, and finally the highly associated anisotropic ψ-DNA is produced. Conditions are given under which the sequence B ? Z ? “U” ψ(+) can be stopped at any point in the direction from left to right. The reverse processes, from right to left, occur when ψ(+) or “U”-DNA are treated with various amounts of salt concentrations and lowering temperature. Thus it is demonstrated that four conformers of poly(dGdC) · poly(dGdC) are readily interconvertible, and that Z-DNA and “U” conformers are intermediates in the reversible transformations of B- and ψ-DNA.