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A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important lipid intermediate and signaling lipid at the branch point of these pathways and constantly monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. Here, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for the selective binding to membranes containing PA over phosphatidylserine (PS). The insertion of the AH into the hydrophobic core of the membrane renders Opi1 sensitive to the lipid acyl chain composition as an important factor contributing to the regulation of membrane biogenesis. Based on these findings, we rationally designed the membrane binding properties of Opi1 to control its responsiveness in the physiological context. Using extensive molecular dynamics (MD) simulations, we identified two PA-selective three-finger grips that tightly bind the phosphate headgroup, while interacting less intimately and more transiently with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.
A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important intermediate at the branch point of these pathways and is continuously monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. In this study, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for selective binding of PA over phosphatidylserine (PS). The insertion of the AH into the membrane core renders Opi1 sensitive to the lipid acyl chain composition and provides a means to adjust membrane biogenesis. By rational design of the AH, we tune the membrane-binding properties of Opi1 and control its responsiveness in vivo. Using extensive molecular dynamics simulations, we identify two PA-selective three-finger grips that tightly bind the PA phosphate headgroup while interacting less intimately with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.
Wie drückend waren die Zensurverhältnisse im 18. Jahrhundert? Für das territorial zersplitterte Deutschland jener Epoche wird man eine flächendeckend zutreffende Antwort nicht geben können; überraschend aber, wie klar sich der Buchhandel zu dieser Frage geäußert hat: Friedrich Perthes zufolge herrschte damals die "vollständigste Preßfreiheit, der Sache und der That nach". Das Rätsel dieser rückhaltlos positiven Bewertung löst sich im Blick auf die durchgehend glimpfliche Behandlung, die Buchhändler in Zensurangelegenheiten erfahren haben: Ihnen kam zugute, dass der Buchhandel inzwischen zu einem bedeutenden Wirtschaftsfaktor aufgestiegen war und jede Einschränkung seiner Tätigkeit durch obrigkeitliche Kommunikationskontrolle unter Gesichtspunkten des merkantilistischen Territorialinteresses unerwünscht sein musste. Dieser Antagonismus zwischen Ökonomie und Zensur spiegelt sich auch in den kameralistisch-gewerbepolitischen Argumentationsmustern, die für die Behörden handlungsleitend geworden waren und dem Buchhandel – jedenfalls bis zur Französischen Revolution – beträchtliche Freiräume verschafft haben. Der Beitrag gibt den Blick frei auf einen Problemzusammenhang, der in der (immer noch stark vorurteilsbehafteten) Zensurgeschichtsschreibung häufig übersehen wird.
New results from the energy scan programme of NA49, in particular kaon production at 30 AGeV and phi production at 40 and 80 AGeV are presented. The K+/pi+ ratio shows a pronounced maximum at 30 AGeV; the kaon slope parameters are constant at SPS energies. Both findings support the scenario of a phase transition at about 30 AGeV beam energy. The phi/pi ratio increases smoothly with beam energy, showing an energy dependence similar to K-/pi-. The measured particle yields can be reproduced by a hadron gas model, with chemical freeze-out parameters on a smooth curve in the T-muB plane. The transverse spectra can be understood as resulting from a rapidly expanding, locally equilibrated source. No evidence for an earlier kinetic decoupling of heavy hyperons is found.
We present the first measurement of fluctuations from event to event in the production of strange particles in collisions of heavy nuclei. The ratio of charged kaons to charged pions is determined for individual central Pb+Pb collisions. After accounting for the fluctuations due to detector resolution and finite number statistics we derive an upper limit on genuine non-statistical fluctuations, perhaps related to a first or second order QCD phase transition. Such fluctuations are shown to be very small.
The large acceptance and high momentum resolution as well as the significant particle identification capabilities of the NA49 experiment at the CERN SPS allow for a broad study of fluctuations and correlations in hadronic interactions. In the first part recent results on event-by-event charge and p_t fluctuations are presented. Charge fluctuations in central Pb+Pb reactions are investigated at three different beam energies (40, 80, and 158 AGeV), while for the p_t fluctuations the focus is put on the system size dependence at 158 AGeV. In the second part recent results on Bose Einstein correlations of h-h- pairs in minimum bias Pb+Pb reactions at 40 and 158 AGeV, as well as of K+K+ and K-K- pairs in central Pb+Pb collisions at 158 AGeV are shown. Additionally, other types of two particle correlations, namely pi p, Lambda p, and Lambda Lambda correlations, have been measured by the NA49 experiment. Finally, results on the energy and system size dependence of deuteron coalescence are discussed.
Rapidity distributions for Lambda and anti-Lambda hyperons in central Pb-Pb collisions at 40, 80 and 158 AGeV and for K 0 s mesons at 158 AGeV are presented. The lambda multiplicities are studied as a function of collision energy together with AGS and RHIC measurements and compared to model predictions. A different energy dependence of the Lambda/pi and anti-Lambda/pi is observed. The anti-Lambda/Lambda ratio shows a steep increase with collision energy. Evidence for a anti-Lambda/anti-p ratio greater than 1 is found at 40 AGeV.
The energy dependence of hadron production in central Pb+Pb collisions is presented and discussed. In particular, midrapidity m_T-spectra for pi-, K-, K+, p, bar p, d, phi, Lambda and bar Lambda at 40, 80 and 158 AGeV are shown. In addition Xi and Omega spectra are available at 158 AGeV. The spectra allow to determine the thermal freeze-out temperature T and the transverse flow velocity beta_T at the three energies. We do not observe a significant energy dependence of these parameters; furthermore there is no indication of early thermal freeze-out of Xi and Omega at 158 AGeV. Rapidity spectra for pi-, K-, K+ and phi at 40, 80 and 158 AGeV are shown, as well as first results on Omega rapidity distributions at 158 AGeV. The chemical freeze-out parameters T and mu_B at the three energies are determined from the total yields. The parameters are close to the expected phase boundary in the SPS energy range and above. Using the total yields of kaons and lambdas, the energy dependence of the strangeness to pion ratio is discussed. A maximum in this ratio is found at 40 AGeV. This maximum could indicate the formation of deconfined matter at energies above 40 AGeV. A search for open charm in a large sample of 158 AGeV events is presented. No signal is observed. This result is compared to several model predictions.
Experiment NA49 at the Cern SPS uses a large acceptance detector for a systematic study of particle yields and correlations in nucleus-nucleus, nucleon-nucleus and nucleon-nucleon collisions. Preliminary results for Pb+Pb collisions at 40, 80 and 158 A*GeV beam energy are shown and compared to measurements at lower and higher energies.
Background: To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of MYCN oncogene amplification (MNA). Methods: Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group). Results: Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39–54%) and 56% (95%-CI 49–63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18–31%, p < 0.001; OS 32% 95%-CI 25–39%, p < 0.001). The presence of RAS-/p53-pathway gene alterations was associated with impaired 10-year EFS and OS (19% vs. 55%, and 19% vs. 67%, respectively; both p < 0.001). In time-dependent multivariable analyses, alterations of RAS-/p53-pathway genes and the extent of the best primary tumor resection were the only independent prognostic variables for OS (p < 0.001 and p = 0.011, respectively). Conclusions: Neuroblastoma patients attributed to high risk solely by MYCN amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.