Origins of Chevron Rollovers in Non-Two-State Protein Folding Kinetics

Chevron rollovers of some proteins imply that their logarithmic folding rates are nonlinear in native stability. This is predicted by lattice and continuum G\=o models to arise from diminished accessibilities of the ground state from transiently populated compact conformations under strongly native conditions. Despite these models' native-centric interactions, the slowdown is due partly to kinetic trapping caused by some of the folding intermediates' nonnative topologies. Notably, simple two-state folding kinetics of small single-domain proteins are not reproduced by common G\=o-like schemes.Comment: 10 pages, 4 Postscript figures (will appear on PRL

Аналіз тенденцій рівня розвитку економічних процесів підприємства

Подано методичні розробки щодо визначення ймовірної зміни рівнів розвитку економічних процесів машинобудівних підприємств залежно від рівня ефективності матеріальної мотивації персоналу на період 2010 р. Імовірну зміну рівня розвитку економічного процесу визначено за допомогою ланцюгів Маркова, що передбачає реалізацію шести послідовних етапів. Ключові слова: підприємства машинобудування, ланцюги Маркова, економічні процеси.Представлены методические разработки по определению вероятного изменения уровня развития экономических процессов предприятий машиностроения в зависимости от уровня эффективности материальной мотивации персонала на период 2010 г. Вероятное изменение уровня развития экономического процесса определено с помощью цепей Маркова, что предусматривает реализацию шести последовательных этапов. Ключевые слова: предприятия машино-стро¬ения, цепи Маркова, экономические процессы.The paper presents methodical developments on determination of probable changes in the level of machine-build enterprises’ economic processes development depending on the level of personnel’s material motivation efficiency for the period of 2010. Probable changes in the level of economic processes development are determined by using Markov’s chains which provide six stages. Keywords: machine-building enterprises, Markov chains, economic processes

Characterization of the molecular environment of the protein tyrosine phosphatase PTP-BL

Contains fulltext : 18735.pdf (publisher's version ) (Open Access)177 p

No Evidence for Involvement of Mouse Protein-tyrosine Phosphatase-BAS-like Fas-associated Phosphatase-1 in Fas-mediated Apoptosis

Contains fulltext : 24530___.PDF (publisher's version ) (Open Access

The neuronal nitric oxide synthase PDZ motif binds to -G(D,E)XV* carboxyterminal sequences

Contains fulltext : 25057___.PDF (publisher's version ) (Open Access

No Evidence for Involvement of Mouse Protein-tyrosine Phosphatase-BAS-like Fas-associated Phosphatase-1 in Fas-mediated Apoptosis

Contains fulltext : 216420.pdf (Publisher’s version ) (Open Access)6 p

Complete knockout of the nociceptin/orphanin FQ receptor in the rat does not induce compensatory changes in mu, delta and kappa opioid receptors.

The nociceptin/orphanin FQ (N/OFQ) opioid peptide receptor (NOPr) is a new member of the opioid receptor family consisting of mu, delta and kappa opioid receptors. The anti-opioid properties of its endogenous ligand, N/OFQ provide the receptor interesting potentials in symptoms and processes related to drug addiction, learning and memory, anxiety and depression, and nociception. Using target-selected N-ethyl-N-nitrosourea (ENU)-driven mutagenesis we recently generated a rat model bearing a premature stop codon in the opioid-like receptor (oprl1) gene, and here we describe the primary characterization of this novel model. Data revealed that [(3)H]N/OFQ binding to brain slices was completely absent in rats homozygous for the premature stop codon (oprl1(-/-)). Heterozygous rats displayed an intermediate level of NOPr binding. Oprl1 receptor transcript levels, as determined by Northern blot analysis, were reduced by approximately 50% in oprl1(-/-) rats compared to wild-type controls (oprl1(+/+)), and no alternative spliced transcripts were observed. Quantitative autoradiographic mapping of mu, delta and kappa opioid receptors using [(3)H]DAMGO, [(3)H]deltorphin and [(3)H]CI-977, respectively, did not show any changes in opioid receptor binding. In conclusion, we present a novel mutant rat lacking NOPr without compensatory changes in mu, delta and kappa opioid receptors. We anticipate that this mutant rat will have heuristic value to further understand the function of NOPr.

A FERM domain governs apical confinement of PTP-BL in epithelial cells

PTP-BL is a cytosolic multidomain protein tyrosine phosphatase that shares homologies with several submembranous and tumor suppressor proteins. Here we show, by transient expression of modular protein domains of PTP-BL in epithelial MDCK cells, that the presence of a FERM domain in the protein is both necessary and sufficient for its targeting to the apical side of epithelial cells. Furthermore, immuno-electron microscopy on stable expressing MDCK pools, that were obtained using an EGFP-based cell sorting protocol, revealed that FERM domain containing fusion proteins are enriched in microvilli and have a typical submembranous location at about 10-15 nm from the plasma membrane. Immunofluorescence microscopy suggested colocalization of the FERM domain moiety with the membrane-cytoskeleton linker ezrin. However, at the electron microscopy level this colocalization cannot be confirmed nor can we detect a direct interaction by immunoprecipitation assays. Fluorescence recovery after photobleaching (FRAP) experiments show that PTP-BL confinement is based on a dynamic steady state and that complete redistribution of the protein may occur within 20 minutes. Our observations suggest that relocation is mediated via a cytosolic pool, rather than by lateral movement. Finally, we show that PTP-BL phosphatase domains are involved in homotypic interactions, as demonstrated by yeast two-hybrid assays. Both the highly restricted subcellular compartmentalization and its specific associative properties may provide the appropriate conditions for regulating substrate specificity and catalytic activity of this member of the PTP family

Microalterations of inherently unstable genomic regions in rat mammary carcinomas as revealed by long oligonucleotide array-based comparative genomic hybridization

The presence of copy number variants in normal genomes poses a challenge to identify small genuine somatic copy number changes in high-resolution cancer genome profiling studies due to the use of unpaired reference DNA. Another problem is the well-known rearrangements of immunoglobulin and T-cell receptor genes in lymphocytes (a commonly used reference), which may misdirect the researcher to a locus with no relevance in tumorigenesis. We here show real gains of the IgG heavy chain V gene region in carcinogen-induced rat mammary tumor samples after normalization to paired mammary gland, a tissue without lymphocyte infiltration. We further show that the segmental duplication region encompassing the IgG heavy chain V genes is a copy number variant between the susceptible (SS) and the resistant (BN) to mammary tumor development inbred rat strains. Our data suggest that the already inherently unstable genomic region is a convenient target for additional structural rearrangements (gains) at the somatic level when exposed to a carcinogen (7,12-dimethylbenz[a]anthracene), which subsequently seem to benefit tumor development in the mammary gland of the susceptible strain. Thus, the selection of an appropriate reference DNA enabled us to identify immunoglobulin genes as novel cancer targets playing a role in mammary tumor development. We conclude that control DNA in array-based comparative genomic hybridization experiments should be selected with care, and DNA from pooled spleen (contains immature lymphocytes and is used as reference in animal studies) or blood may not be the ideal control in the study of primary tumors.