The MX-Helix of Muscle nAChR Subunits Regulates Receptor Assembly and Surface Trafficking.

Nicotinic acetylcholine receptors (AChRs) are pentameric channels that mediate fast transmission at the neuromuscular junction (NMJ) and defects in receptor expression underlie neuromuscular disorders such as myasthenia gravis and congenital myasthenic syndrome (CMS). Nicotinic receptor expression at the NMJ is tightly regulated and we previously identified novel Golgi-retention signals in the β and δ subunit cytoplasmic loops that regulate trafficking of the receptor to the cell surface. Here, we show that the Golgi retention motifs are localized in the MX-helix, a juxta-membrane alpha-helix present in the proximal cytoplasmic loop of receptor subunits, which was defined in recent crystal structures of cys-loop receptor family members. First, mutational analysis of CD4-MX-helix chimeric proteins showed that the Golgi retention signal was dependent on both the amphipathic nature of the MX-helix and on specific lysine residues (βK353 and δK351). Moreover, retention was associated with ubiquitination of the lysines, and βK353R and δK351R mutations reduced ubiquitination and increased surface expression of CD4-β and δ MX-helix chimeric proteins. Second, mutation of these lysines in intact β and δ subunits perturbed Golgi-based glycosylation and surface trafficking of the AChR. Notably, combined βK353R and δK351R mutations increased the amount of surface AChR with immature forms of glycosylation, consistent with decreased Golgi retention and processing. Third, we found that previously identified CMS mutations in the ε subunit MX-helix decreased receptor assembly and surface levels, as did an analogous mutation introduced into the β subunit MX-helix. Together, these findings indicate that the subunit MX-helix contributes to receptor assembly and is required for normal expression of the AChR and function of the NMJ. In addition, specific determinants in the β and δ subunit MX-helix contribute to quality control of AChR expression by intracellular retention and ubiquitination of unassembled subunits, and by facilitating the appropriate glycosylation of assembled surface AChR

Är konsumtion alltid rationell? -med rökning som exempel

The microeconomic literature has for a long time asserted that homos economicus act ration-ally i.e. the choices she makes in life are based upon the fact that she always seeks to maxim-ize her own welfare. By the available information she is capable of calculating which alterna-tive of consumption possibilities that gives her the highest utility subject to its costs and hence, she always makes optimal choices. The assumption is foundation for most economic models on consumption and these models are in turn used as bases for political decisions. Research and empirical facts show however that not all types of consumption follow this ra-tional pattern, which may have implications for political decision making. By introducing modern behavioral economic theory I aim to show the importance of new theory as an alterna-tive to the traditional in the cases where it fails to explain certain consumption behaviors. The analysis is applied to a framework of addictive goods and cigarette consumption in particular, where the behavioral approach proves inconsistency. This fact changes the results of incidence analysis on excise taxes on cigarettes and has in fact quite different implications for political decision making than do the rational approach

AS EXPORTAÇOES BRASILEIRAS DA SOJA EM GRÃO PARA A CHINA NO PERIODO DE 1995 A 2005.

O presente artigo tem como finalidade avaliar a competitividade da soja em grão brasileira para a China e verificar sua orientação regional entre 1995 e 2005. Desta forma partiu-se de uma análise acerca da inserção nacional no comércio da Soja enfatizando a especificidade Brasil-China e posteriormente efetuou-se o cálculo do Índice de Vantagens Comparativas Reveladas e o Índice de Orientação Regional. Os resultados da análise demonstraram que o Brasil possui vantagens comparativas reveladas nas exportações de soja em grão para a China no período dos dez anos sendo estes crescentes com exceção os anos de 1999 2001 e 2003. O Índice de Orientação regional demonstrou que as exportações brasileiras de soja em grão estão sendo direcionadas para a China a partir do ano de 1997 mas não de modo crescentes. Assim, pode-se dizer que a análise estabelecida foi corroborada pelos resultados encontrados e conseqüentemente trás uma perspectiva de crescimento do intercâmbio comercial brasileiro com a China. -------------------------------------------The present work aims at evaluating the competitiveness of Brazilian soybean grains to China and to verify its regional orientation between 1995 and 2005. In this way we began a analysis about the national insertion in the soybean commerce emphasizing the peculiarity Brazil-China and afterwards we performed the calculation of the Revealed Comparative Advantage Index and the Regional Orientation Index. The analysis results demonstrated that Brazil has revealed comparative advantages in the exportation of soybean grains to China in the ten years of the considered period and those were increasing except in the years of 1999 2001 and 2003. The Regional orientation Index demonstrated that the Brazilian exportation of soybean grains is being direct to Chine since 1997 but not in an increasing way. Thus we can say that the established analysis was corroborated by the findings and consequently it brings a perspective of an increasing in the Brazilian commercial interchange with China.Soja, Comércio Internacional, China, Soybean, International Commerce, China, International Relations/Trade,

The Influence Of Romantic Poetry On The Career And Music Of Nicolas Medtner

Nicolas Medtner was a composer born out of his time. He was a true Romantic in the Russian Silver Age and his creative ideology owes much to the Romantic poetry that he was devoted to all his life. This poetry put a decisive stamp on his music and influenced his career decisions. Medtner was exposed to the most renowned literature from an early age. Influenced by his father, and his oldest brother Emil, he developed a lifelong love for literature and especially poetry. Literary connections are apparent throughout Medtner’s music, including (and not limited to) references to Goethe, Pushkin, Lermontov, Tyutchev, Fet, Nietzsche, and Shakespeare. The influence of poetry on his personality, philosophy, and piano compositions is discussed in this document. A clearer understanding of the intrinsic connections Medtner’s music has with poetry will further aid the enjoyment of the listener and help the performer conceive an imaginative and effective interpretation of Medtner’s piano music

The Effect of Group Counseling on Visual Imagery and Selected Personality Factors for Junior and Senior Level High School Students

The problem of this study was to measure the effect of group counseling on visual imagery and selected personality factors of junior and senior level secondary school students. The purpose of this study was to determine if perception of visual images changed after group counseling. Also investigated was whether a concomital relationship existed among the perception of visual images and the self-concept, ascendance, and sociability

Voting Rights & Felon Disenfranchisement: A New Path Forward

The current felon disenfranchisement policies in Minnesota undermine the essential voting rights necessary for democracy to thrive. Minnesota currently outranks many founding NATO countries in incarceration rates per 100,000 in population. If an individual in Minnesota is convicted of a felony, their right to vote is revoked until they complete their sentence, probation, or parole. This is especially problematic because Minnesota’s probationary periods extend into decades long punitive measures. Governor Mark Dayton’s Task Force suggestions of allowing felons to vote after incarceration is a step in the right direction, but does not go far enough to alleviate the problem of felon disenfranchisement. In order to correct this unjust policy of felon disenfranchisement, we recommend a new path forward: (1) A total reform of felon disenfranchisement policies in Minnesota by automatically restoring the voting rights to felons currently incarcerated, and those on probation and parole, (2) Criminal defendants are to be informed of their right to vote upon their immediate restoration and that they are eligible to register to vote, and (3) The Department of Corrections and Probation and Parole authorities responsible for assisting with voluntary voter registration, ensuring all citizens are subject to the same application procedures

Targeted Metabolic Profiling Indicates Apple Rootstock Genotype-Specific Differences in Primary and Secondary Metabolite Production and Validate Quantitative Contribution From Vegetative Growth

Previous reports regarding rhizodeposits from apple roots are limited, and complicated by microbes, which readily colonize root systems and contribute to modify rhizodeposit metabolite composition. This study delineates methods for collection of apple rhizodeposits under axenic conditions, indicates rootstock genotype-specific differences and validates the contributions of vegetative activity to rhizodeposit quantity. Primary and phenolic rhizodeposit metabolites collected from two apple rootstock genotypes, G935 and M26, were delineated 2 months after root initiation by utilizing gas chromatography/liquid chromatography—mass spectrometry (GC/LC-MS), respectively. Twenty-one identified phenolic compounds and 29 sugars, organic acids, and amino acids, as well as compounds tentatively identified as triterpenoids were present in the rhizodeposits. When adjusted for whole plant mass, hexose, erythrose, galactose, phloridzin, kaempferol-3-glucoside, as well as glycerol, and glyceric acid differed between the genotypes. Phloridzin, phloretin, epicatechin, 4-hydroxybenzoic acid, and chlorogenic acid were among the phenolic compounds found in higher relative concentration in rhizodeposits, as assessed by LC-MS. Among primary metabolites assessed by GC-MS, amino acids, organic acids, and sugar alcohols found in relatively higher concentration in the rhizodeposits included L-asparagine, L-cysteine, malic acid, succinic acid, and sorbitol. In addition, putative ursane triterprenoids, identified based on accurate mass comparison to previously reported triterpenoids from apple peel, were present in rhizodeposits in high abundance relative to phenolic compounds assessed via the same extraction/instrumental method. Validation of metabolite production to tree vegetative activity was conducted using a separate set of micropropagated trees (genotype MM106) which were treated with a toxic volatile compound (butyrolactone) to inhibit activity/kill leaves and vegetative growth. This treatment resulted in a reduction of total collected rhizodeposits relative to an untreated control, indicating active vegetative growth contributes to rhizodeposit metabolites. Culture-based assays indicated an absence of bacterial or fungal endophytes in roots of micropropagated G935 and M26 plants. However, the use of fungi-specific primers in qPCR indicated the presence of fungal DNA in 30% of the samples, thus the contribution of endophytes to rhizodeposits cannot be fully eliminated. This study provides fundamental information for continued research and application of rhizosphere ecology driven by apple rootstock genotype specific rhizodeposition