Identification of the mitochondrial receptor complex in Saccharomyces cerevisiae

Mitochondrial protein import involves the recognition of preproteins by receptors and their subsequent translocation across the outer membrane. In Neurospora crassa, the two import receptors, MOM19 and MOM72, were found in a complex with the general insertion protein, GIP (formed by MOM7, MOM8, MOM30 and MOM38) and MOM22. We isolated a complex out of S. cerevisiae mitochondria consisting of MOM38/ISP42, the receptor MOM72, and five new yeast proteins, the putative equivalents of N. crassa MOM7, MOM8, MOM19, MOM22 and MOM30. A receptor complex isolated out of yeast cells transformed with N. crassa MOM19 contained the N. crassa master receptor in addition to the yeast proteins. This demonstrates that the yeast complex is functional, and provides strong evidence that we also have identified the yeast MOM19

Import of ADP/ATP carrier into mitochondria

We have identified the yeast homologue of Neurospora crassa MOM72, the mitochondrial import receptor for the ADP/ATP carrier (AAC), by functional studies and by cDNA sequencing. Mitochondria of a yeast mutant in which the gene for MOM72 was disrupted were impaired in specific binding and import of AAC. Unexpectedly, we found a residual, yet significant import of AAC into mitochondria lacking MOM72 that occurred via the receptor MOM19. We conclude that both MOM72 and MOM19 can direct AAC into mitochondria, albeit with different efficiency. Moreover, the precursor of MOM72 apparently does not require a positively charged sequence at the extreme amino terminus for targeting to mitochondria

Налогообложение дорожного движения в Германии: современные проблемы и планы реформирования

Статья посвящена изучению налогообложения дорожного движения в Германии и разработке предложений по его реформированию. В исследовании использован политико-ориентированный подход, соединяющий фискальную теорию и фискальную практику. Данный подход продолжает традиции таких исследователей как Ричард Масгрейв (США) и Гюнтер Шмольдер (Германия). Поставлен вопрос о соответствие налогообложения дорожного движения в Германии трем основным принципам налогообложения: справедливости, эффективности и практичности. Первоначально рассматривается, каким образом может налогообложение дорожного движения воплощать данные принципы, а затем, анализируется соответствие этим принципам налогов и сборов, составляющих систему налогообложения дорожного движения в Германии. Рассматриваются два налога (энергетический налог и налог на автотранспорт) и два сбора (дорожный сбор для грузовых транспортных средств и плата за инфраструктуру). Сделан вывод, что ни один из представленных налогов и сборов не соответствует основным принципам налогообложения. На основе исследования предлагается реформирование налогов и сборов, связанных с дорожным движением в Германии. Анализируются перспективы предлагаемых изменений, их фискальные и экономические последствия. Предлагаемые изменения обсуждаются как с точки зрения их справедливости и эффективности, так и с точки зрения политической приемлемости и совместимости с европейским законодательством. Установлено, что предложенная реформа соответствует принципам налогообложения и европейского права, но труднореализуема в настоящее время.This article examines the taxation of road traffic in Germany and makes a proposal for its reform. The policy-oriented approach used here is inspired by the tradition of economists like Richard A. Musgrave in the United States or Günter Schmölders in Germany who always sought to integrate fiscal theory and fiscal practice. Thus, our considerations are guided by three basic principles of taxation which are well-founded theoretically and, at the same time, flexible enough to deal with issues of policy: fairness, efficiency and practicability. They are used, at first, to show what a systematic taxation of road traffic would look like. Then, actual road traffic taxation in Germany is described and measured against this standard. It turns out that none of the different road traffic taxes or fees in Germany conform to the principles of taxation. Therefore, finally, a proposal for reform is made which is discussed not only in terms of fairness and efficiency but also in terms of political acceptability and of compatibility with European law. It is found that the reform proposed complies with the principles of taxation and European law, but that, at present, it may be difficult to win public acceptance for one of its parts.The helpful comments of Igor Mayburov and two anonymous referees are gratefully acknowledgedАвтор признателен Игорю Майбурову и двум анонимным рецензентам за полезные комментари

Rational climate policy - economic demands and political obstacles

In der klimapolitischen Debatte stehen meist einzelne Instrumente und Maßnahmen im Vordergrund, wohingegen die Frage der ökonomischen Rationalität der Klimapolitik als solcher häufig vernachlässigt wird. Eine Klimapolitik wäre dann ökonomisch rational, wenn politisch vorgegebene Klimaziele mit geringstmöglichen Kosten realisiert werden würden. Notwendig hierfür ist eine umfassende und einheitliche Bepreisung der Treibhausgasemissionen. Dieser rationalen Klimapolitik wird die aktuelle deutsche und europäische Politik gegenübergestellt, die sich als ineffektiv und ineffizient erweist. Ursächlich hierfür sind die Anreize, denen die politischen Akteure unterliegen und die zu einem Widerspruch zwischen ökonomischer Rationalität und politischer Opportunität führen.The debate about climate policy is mainly concerned with particular measures and instruments. Only rarely is the economic rationality of climate policy as such discussed. Climate policy would be economically rational, if climate objectives, which are to be determined politically, are realized with minimum costs. To this end, a comprehensive and uniform price on the emission of greenhouse gases has to be established. The actual climate policy, in Germany and in Europe, is far from being economically rational: It is both ineffective and inefficient. This is due to political incentives which make inefficient policies politically more attractive than efficient ones

In silico design and performance of peptide microarrays for breast cancer tumour-auto-antibody testing

The simplicity and potential of minimally invasive testing using sera from patients makes auto-antibody based biomarkers a very promising tool for use in cancer diagnostics. Protein microarrays have been used for the identification of such auto-antibody signatures. Because high throughput protein expression and purification is laborious, synthetic peptides might be a good alternative for microarray generation and multiplexed analyses. In this study, we designed 1185 antigenic peptides, deduced from proteins expressed by 642 cDNA expression clones found to be sero-reactive in both breast tumour patients and controls. The sero-reactive proteins and the corresponding peptides were used for the production of protein and peptide microarrays. Serum samples from females with benign and malignant breast tumours and healthy control sera (n=16 per group) were then analysed. Correct classification of the serum samples on peptide microarrays were 78% for discrimination of ‘malignant versus healthy controls’, 72% for ‘benign versus malignant’ and 94% for ‘benign versus controls’. On protein arrays, correct classification for these contrasts was 69%, 59% and 59%, respectively. The over-representation analysis of the classifiers derived from class prediction showed enrichment of genes associated with ribosomes, spliceosomes, endocytosis and the pentose phosphate pathway. Sequence analyses of the peptides with the highest sero-reactivity demonstrated enrichment of the zinc-finger domain. Peptides’ sero-reactivities were found negatively correlated with hydrophobicity and positively correlated with positive charge, high inter-residue protein contact energies and a secondary structure propensity bias. This study hints at the possibility of using in silico designed antigenic peptide microarrays as an alternative to protein microarrays for the improvement of tumour auto-antibody based diagnostics

Chirality of nanophotonic waveguide with embedded quantum emitter for unidirectional spin transfer

Scalable quantum technologies may be achieved by faithful conversion between matter qubits and photonic qubits in integrated circuit geometries. Within this context, quantum dots possess well-defined spin states (matter qubits), which couple efficiently to photons. By embedding them in nanophotonic waveguides, they provide a promising platform for quantum technology implementations. In this paper, we demonstrate that the naturally occurring electromagnetic field chirality that arises in nanobeam waveguides leads to unidirectional photon emission from quantum dot spin states, with resultant in-plane transfer of matter-qubit information. The chiral behaviour occurs despite the non-chiral geometry and material of the waveguides. Using dot registration techniques, we achieve a quantum emitter deterministically positioned at a chiral point and realize spin-path conversion by design. We further show that the chiral phenomena are much more tolerant to dot position than in standard photonic crystal waveguides, exhibit spin-path readout up to 95±5% and have potential to serve as the basis of spin-logic and network implementations

Direct observation of free-exciton thermalization in quantum-well structures

We report on a direct observation of free-exciton thermalization in quantum-well structures. A narrow energy distribution of free 1s excitons is created in ZnSe-based quantum wells by emission of one LO phonon after optical excitation of the continuum states with picosecond laser pulses. The subsequent relaxation dynamics within the 1s-exciton dispersion is directly monitored by time-resolved studies of the phonon-assisted photoluminescence. It is demonstrated that the free-exciton distribution remains nonthermal for some 100 ps. The observed dynamics is in reasonable agreement with numerical results of a rate-equation model which accounts for the relevant exciton-phonon coupling mechanisms

Analysis of SEC9 Suppression Reveals a Relationship of SNARE Function to Cell Physiology

BACKGROUND:Growth and division of Saccharomyces cerevisiae is dependent on the action of SNARE proteins that are required for membrane fusion. SNAREs are regulated, through a poorly understood mechanism, to ensure membrane fusion at the correct time and place within a cell. Although fusion of secretory vesicles with the plasma membrane is important for yeast cell growth, the relationship between exocytic SNAREs and cell physiology has not been established. METHODOLOGY/PRINCIPAL FINDINGS:Using genetic analysis, we identified several influences on the function of exocytic SNAREs. Genetic disruption of the V-ATPase, but not vacuolar proteolysis, can suppress two different temperature-sensitive mutations in SEC9. Suppression is unlikely due to increased SNARE complex formation because increasing SNARE complex formation, through overexpression of SRO7, does not result in suppression. We also observed suppression of sec9 mutations by growth on alkaline media or on a non-fermentable carbon source, conditions associated with a reduced growth rate of wild-type cells and decreased SNARE complex formation. CONCLUSIONS/SIGNIFICANCE:Three main conclusions arise from our results. First, there is a genetic interaction between SEC9 and the V-ATPase, although it is unlikely that this interaction has functional significance with respect to membrane fusion or SNAREs. Second, Sro7p acts to promote SNARE complex formation. Finally, Sec9p function and SNARE complex formation are tightly coupled to the physiological state of the cell

VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission

Synaptic vesicles in the brain harbor several soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) proteins. With the exception of synaptobrevin2, or VAMP2 (syb2), which is directly involved in vesicle fusion, the role of these SNAREs in neurotransmission is unclear. Here we show that in mice syb2 drives rapid Ca2+-dependent synchronous neurotransmission, whereas the structurally homologous SNARE protein VAMP4 selectively maintains bulk Ca2+-dependent asynchronous release. At inhibitory nerve terminals, up- or downregulation of VAMP4 causes a correlated change in asynchronous release. Biochemically, VAMP4 forms a stable complex with SNAREs syntaxin-1 and SNAP-25 that does not interact with complexins or synaptotagmin-1, proteins essential for synchronous neurotransmission. Optical imaging of individual synapses indicates that trafficking of VAMP4 and syb2 show minimal overlap. Taken together, these findings suggest that VAMP4 and syb2 diverge functionally, traffic independently and support distinct forms of neurotransmission. These results provide molecular insight into how synapses diversify their release properties by taking advantage of distinct synaptic vesicle–associated SNAREs