Model for eukaryotic tail-anchored protein binding based on the structure of Get3

The Get3 ATPase directs the delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (ER). TA-proteins are characterized by having a single transmembrane helix (TM) at their extreme C terminus and include many essential proteins, such as SNAREs, apoptosis factors, and protein translocation components. These proteins cannot follow the SRP-dependent co-translational pathway that typifies most integral membrane proteins; instead, post-translationally, these proteins are recognized and bound by Get3 then delivered to the ER in the ATP dependent Get pathway. To elucidate a molecular mechanism for TA protein binding by Get3 we have determined three crystal structures in apo and ADP forms from Saccharomyces cerevisae (ScGet3-apo) and Aspergillus fumigatus (AfGet3-apo and AfGet3-ADP). Using structural information, we generated mutants to confirm important interfaces and essential residues. These results point to a model of how Get3 couples ATP hydrolysis to the binding and release of TA-proteins

Excitation function of elliptic flow in Au+Au collisions and the nuclear matter equation of state

We present measurements of the excitation function of elliptic flow at midrapidity in Au+Au collisions at beam energies from 0.09 to 1.49 GeV per nucleon. For the integral flow, we discuss the interplay between collective expansion and spectator shadowing for three centrality classes. A complete excitation function of transverse momentum dependence of elliptic flow is presented for the first time in this energy range, revealing a rapid change with incident energy below 0.4 AGeV, followed by an almost perfect scaling at the higher energies. The equation of state of compressed nuclear matter is addressed through comparisons to microscopic transport model calculations.Comment: 10 pages, 4 eps figures, submitted for publication. Data files will be available at http://www.gsi.de/~fopiwww/pub

Effects of non‐steroidal anti‐inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses. EAACI task force on eicosanoids consensus report in times of COVID‐19

Non‐steroidal anti‐inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti‐inflammatory, antipyretic, and analgesic effects are applied against symptoms of respiratory infections, including SARS‐CoV‐2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID‐19 also revealed the gaps in our understanding of their mechanism of action, selectivity, and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs‐exacerbated respiratory disease (NERD). In this context, the consensus report summarizes currently available knowledge, novel discoveries, and controversies regarding the use of NSAIDs in COVID‐19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID‐19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarize the major knowledge gaps and unmet needs in current eicosanoid research

Tracing the Evolution of Temperature in Near Fermi Energy Heavy Ion Collisions

The kinetic energy variation of emitted light clusters has been employed as a clock to explore the time evolution of the temperature for thermalizing composite systems produced in the reactions of 26A, 35A and 47A MeV $^{64}$Zn with $^{58}$Ni, $^{92}$Mo and $^{197}$Au. For each system investigated, the double isotope ratio temperature curve exhibits a high maximum apparent temperature, in the range of 10-25 MeV, at high ejectile velocity. These maximum values increase with increasing projectile energy and decrease with increasing target mass. The time at which the maximum in the temperature curve is reached ranges from 80 to 130 fm/c after contact. For each different target, the subsequent cooling curves for all three projectile energies are quite similar. Temperatures comparable to those of limiting temperature systematics are reached 30 to 40 fm/c after the times corresponding to the maxima, at a time when AMD-V transport model calculations predict entry into the final evaporative or fragmentation stage of de-excitation of the hot composite systems. Evidence for the establishment of thermal and chemical equilibrium is discussed.Comment: 9 pages, 5 figure

Isotopic Dependence of the Nuclear Caloric Curve

The A/Z dependence of projectile fragmentation at relativistic energies has been studied with the ALADIN forward spectrometer at SIS. A stable beam of 124Sn and radioactive beams of 124La and 107Sn at 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. Chemical freeze-out temperatures are found to be nearly invariant with respect to the A/Z of the produced spectator sources, consistent with predictions for expanded systems. Small Coulomb effects (\Delta T \approx 0.6 MeV) appear for residue production near the onset of multifragmentation.Comment: 11 pages, 3 figures, accepted for publ. in Phys. Rev. Let

Tracing a phase transition with fluctuations of the largest fragment size: Statistical multifragmentation models and the ALADIN S254 data

A phase transition signature associated with cumulants of the largest fragment size distribution has been identified in statistical multifragmentation models and examined in analysis of the ALADIN S254 data on fragmentation of neutron-poor and neutron-rich projectiles. Characteristics of the transition point indicated by this signature are weakly dependent on the A/Z ratio of the fragmenting spectator source. In particular, chemical freeze-out temperatures are estimated within the range 5.9 to 6.5 MeV. The experimental results are well reproduced by the SMM model.Comment: 7 pages, 3 figures, Proceedings of the International Workshop on Multifragmentation and Related Topics (IWM2009), Catania, Italy, November 2009