359 research outputs found
Laue Gamma-Ray Lenses for Space Astrophysics: Status and Prospects
No full textWe review feasibility studies, technological developments, and the astrophysical prospects for Laue lenses devoted
to hard X-/gamma-ray astronomy observations.</jats:p
A two-domain elevator mechanism for sodium/proton antiport
No full textSodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets2. The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli1, 3, for which both electron microscopy and crystal structures are available4, 5, 6. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein1, 4. Like many Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur7. The only reported NhaA crystal structure so far is of the low pH inactivated form4. Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding1, 8, 9 directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second3, Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general
Kinetic coupling of the respiratory chain with ATP synthase, but not proton gradients, drives ATP production in cristae membranes.
No full textMitochondria have a characteristic ultrastructure with invaginations of the inner membrane called cristae that contain the protein complexes of the oxidative phosphorylation system. How this particular morphology of the respiratory membrane impacts energy conversion is currently unknown. One proposed role of cristae formation is to facilitate the establishment of local proton gradients to fuel ATP synthesis. Here, we determined the local pH values at defined sublocations within mitochondria of respiring yeast cells by fusing a pH-sensitive GFP to proteins residing in different mitochondrial subcompartments. Only a small proton gradient was detected over the inner membrane in wild type or cristae-lacking cells. Conversely, the obtained pH values did barely permit ATP synthesis in a reconstituted system containing purified yeast F1F0 ATP synthase, although, thermodynamically, a sufficiently high driving force was applied. At higher driving forces, where robust ATP synthesis was observed, a P-side pH value of 6 increased the ATP synthesis rate 3-fold compared to pH 7. In contrast, when ATP synthase was coreconstituted with an active proton-translocating cytochrome oxidase, ATP synthesis readily occurred at the measured, physiological pH values. Our study thus reveals that the morphology of the inner membrane does not influence the subcompartmental pH values and is not necessary for robust oxidative phosphorylation in mitochondria. Instead, it is likely that the dense packing of the oxidative phosphorylation complexes in the cristae membranes assists kinetic coupling between proton pumping and ATP synthesis
sj-pdf-1-mpp-10.1177_23814683231225667 – Supplemental material for Understanding Treatment Preferences for Patients with Tricuspid Regurgitation
No full textSupplemental material, sj-pdf-1-mpp-10.1177_23814683231225667 for Understanding Treatment Preferences for Patients with Tricuspid Regurgitation by Vijay Iyer, Nadeen N. Faza, Michael Pfeiffer, Mark Kozak, Brandon Peterson, Mortiz Wyler von Ballmoos, Sarah Mollenkopf, Melissa Mancilla, Diandra Latibeaudiere-Gardner and Michael J. Reardon in MDM Policy & Practice</p
sj-pdf-3-mpp-10.1177_23814683231225667 – Supplemental material for Understanding Treatment Preferences for Patients with Tricuspid Regurgitation
No full textSupplemental material, sj-pdf-3-mpp-10.1177_23814683231225667 for Understanding Treatment Preferences for Patients with Tricuspid Regurgitation by Vijay Iyer, Nadeen N. Faza, Michael Pfeiffer, Mark Kozak, Brandon Peterson, Mortiz Wyler von Ballmoos, Sarah Mollenkopf, Melissa Mancilla, Diandra Latibeaudiere-Gardner and Michael J. Reardon in MDM Policy & Practice</p
sj-pdf-2-mpp-10.1177_23814683231225667 – Supplemental material for Understanding Treatment Preferences for Patients with Tricuspid Regurgitation
No full textSupplemental material, sj-pdf-2-mpp-10.1177_23814683231225667 for Understanding Treatment Preferences for Patients with Tricuspid Regurgitation by Vijay Iyer, Nadeen N. Faza, Michael Pfeiffer, Mark Kozak, Brandon Peterson, Mortiz Wyler von Ballmoos, Sarah Mollenkopf, Melissa Mancilla, Diandra Latibeaudiere-Gardner and Michael J. Reardon in MDM Policy & Practice</p
sj-pdf-4-mpp-10.1177_23814683231225667 – Supplemental material for Understanding Treatment Preferences for Patients with Tricuspid Regurgitation
No full textSupplemental material, sj-pdf-4-mpp-10.1177_23814683231225667 for Understanding Treatment Preferences for Patients with Tricuspid Regurgitation by Vijay Iyer, Nadeen N. Faza, Michael Pfeiffer, Mark Kozak, Brandon Peterson, Mortiz Wyler von Ballmoos, Sarah Mollenkopf, Melissa Mancilla, Diandra Latibeaudiere-Gardner and Michael J. Reardon in MDM Policy & Practice</p
ATP synthesis at physiological nucleotide concentrations.
No full textSynthesis of ATP by the F1F0 ATP synthase in mitochondria and most bacteria is energized by the proton motive force (pmf) established and maintained by respiratory chain enzymes. Conversely, in the presence of ATP and in the absence of a pmf, the enzyme works as an ATP-driven proton pump. Here, we investigate how high concentrations of ATP affect the enzymatic activity of the F1F0 ATP synthase under high pmf conditions, which is the typical situation in mitochondria or growing bacteria. Using the ATP analogue adenosine 5'-O-(1-thiotriphosphate) (ATPαS), we have developed a modified luminescence-based assay to measure ATP synthesis in the presence of millimolar ATP concentrations, replacing an assay using radioactive nucleotides. In inverted membrane vesicles of E. coli, we found that under saturating pmf conditions, ATP synthesis was reduced to ~10% at 5 mM ATPαS. This reduction was reversed by ADP, but not Pi, indicating that the ATP/ADP ratio controls the ATP synthesis rate. Our data suggests that the ATP/ADP ratio ~30 in growing E. coli limits the ATP synthesis rate to ~20% of the maximal rate possible at the applied pmf and that the rate reduction occurs via product inhibition rather than an increased ATP hydrolysis rate
Music Theatre as Labyrinth. Extension of liminality in the production The Navidson Records by Till Wyler von Ballmoos and Tassilo Tesche
No full textFor the 2016 edition of the ‘Münchener Biennale – Festival für Neues Musiktheater’ (Munich Biennale – Festival for New Music Theatre), its new Intendants Daniel Ott and Manos organised a series of preparatory workshops intended to promote the creation of new works. This essay explains the influence that this new form of curating process exerted on the gestation of the production The Navidson Records by Till Wyler von Ballmoos and Tassilo Tesche. Our focus is on investigating the working methods employed in the process of conception and rehearsal: the setting of The Navidson Records was from the start intended to avoid creating fixed performance procedures and instead to create an open space of potential. The author analyses the characteristics of that space with the aid of hypotheses derived from ritual theory. A central role here is played by the concept of liminality, which Victor Turner uses to describe the ritual borderline phase between two stable states. This article demonstrates the tendency of current composed theatre to undermine normative patterns of roles and organisation by means of strategies of liminalization. The potential and the difficulties inherent in participant observation in a creative work process are also discussed here
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