Andreev Molecule in Parallel InAs Nanowires

Coupling individual atoms via tunneling fundamentally changes the state of matter: electrons bound to atomic cores become delocalized resulting in a change from an insulating to a metallic state, as it is well known from the canonical example of solids. A chain of atoms could lead to more exotic states if the tunneling takes place via the superconducting vacuum and can induce topologically protected excitations like Majorana or parafermions. Toward the realization of such artificial chains, coupling a single atom to the superconducting vacuum is well studied, but the hybridization of two sites via the superconductor was not yet reported. The peculiar vacuum of the BCS condensate opens the way to annihilate or generate two electrons from the bulk resulting in a so-called Andreev molecular state. By employing parallel nanowires with an Al superconductor shell, two artificial atoms were created at a minimal distance with an epitaxial superconducting link between. Hybridization via the BCS vacuum was observed between the two artificial atoms for the first time, as a demonstration of an Andreev molecular state.Comment: References were update

A Fast and Simple Contact Printing Approach to Generate 2D Protein Nanopatterns

Protein micropatterning has become an important tool for many biomedical applications as well as in academic research. Current techniques that allow to reduce the feature size of patterns below 1 μm are, however, often costly and require sophisticated equipment. We present here a straightforward and convenient method to generate highly condensed nanopatterns of proteins without the need for clean room facilities or expensive equipment. Our approach is based on nanocontact printing and allows for the fabrication of protein patterns with feature sizes of 80 nm and periodicities down to 140 nm. This was made possible by the use of the material X-poly(dimethylsiloxane) (X-PDMS) in a two-layer stamp layout for protein printing. In a proof of principle, different proteins at various scales were printed and the pattern quality was evaluated by atomic force microscopy (AFM) and super-resolution fluorescence microscopy

Extramitochondrial OPA1 and adrenocortical function

We have previously described that silencing of the mitochondrial protein OPA1 enhances mitochondrial 27 Ca2+ signaling and aldosterone production in H295R adrenocortical cells. Since extramitochondrial OPA1 28 (emOPA1) was reported to facilitate cAMP-induced lipolysis, we hypothesized that emOPA1, via the 29 enhanced hydrolysis of cholesterol esters, augments aldosterone production in H295R cells. A few 30 OPA1 immunopositive spots were detected in �40% of the cells. In cell fractionation studies OPA1/COX 31 IV (mitochondrial marker) ratio in the post-mitochondrial fractions was an order of magnitude higher 32 than that in the mitochondrial fraction. The ratio of long to short OPA1 isoforms was lower in post-mito- 33 chondrial than in mitochondrial fractions. Knockdown of OPA1 failed to reduce db-cAMP-induced phos- 34 phorylation of hormone-sensitive lipase (HSL), Ca2+ signaling and aldosterone secretion. In conclusion, 35 OPA1 could be detected in the post-mitochondrial fractions, nevertheless, OPA1 did not interfere with 36 the cAMP – PKA – HSL mediated activation of aldosterone secretio

Evaluation of a novel magneto-optical method for the detection of malaria parasites

Improving the efficiency of malaria diagnosis is one of the main goals of current malaria research. We have recently developed a magneto-optical (MO) method which allows high-sensitivity detection of malaria pigment (hemozoin crystals) in blood via the magnetically induced rotational motion of the hemozoin crystals. Here, we evaluate this MO technique for the detection of Plasmodium falciparum in infected erythrocytes using in-vitro parasite cultures covering the entire intraerythrocytic life cycle. Our novel method detected parasite densities as low as approximately 40 parasites per microliter of blood (0.0008% parasitemia) at the ring stage and less than 10 parasites/microL (0.0002% parasitemia) in the case of the later stages. These limits of detection, corresponding to approximately 20 pg/microL of hemozoin produced by the parasites, exceed that of rapid diagnostic tests and compete with the threshold achievable by light microscopic observation of blood smears. The MO diagnosis requires no special training of the operator or specific reagents for parasite detection, except for an inexpensive lysis solution to release intracellular hemozoin. The devices can be designed to a portable format for clinical and in-field tests. Besides testing its diagnostic performance, we also applied the MO technique to investigate the change in hemozoin concentration during parasite maturation. Our preliminary data indicate that this method may offer an efficient tool to determine the amount of hemozoin produced by the different parasite stages in synchronized cultures. Hence, it could eventually be used for testing the susceptibility of parasites to antimalarial drugs

The Effect of OPA1 on Mitochondrial Ca2+ Signaling

The dynamin-related GTPase protein OPA1, localized in the intermembrane space and tethered to the inner membrane of mitochondria, participates in the fusion of these organelles. Its mutation is the most prevalent cause of Autosomal Dominant Optic Atrophy. OPA1 controls the diameter of the junctions between the boundary part of the inner membrane and the membrane of cristae and reduces the diffusibility of cytochrome c through these junctions. We postulated that if significant Ca2+ uptake into the matrix occurs from the lumen of the cristae, reduced expression of OPA1 would increase the access of Ca2+ to the transporters in the crista membrane and thus would enhance Ca2+ uptake. In intact H295R adrenocortical and HeLa cells cytosolic Ca2+ signals evoked with K+ and histamine, respectively, were transferred into the mitochondria. The rate and amplitude of mitochondrial [Ca2+] rise (followed with confocal laser scanning microscopy and FRET measurements with fluorescent wide-field microscopy) were increased after knockdown of OPA1, as compared with cells transfected with control RNA or mitofusin1 siRNA. Ca2+ uptake was enhanced despite reduced mitochondrial membrane potential. In permeabilized cells the rate of Ca2+ uptake by depolarized mitochondria was also increased in OPA1-silenced cells. The participation of Na+/Ca2+ and Ca2+/H+ antiporters in this transport process is indicated by pharmacological data. Altogether, our observations reveal the significance of OPA1 in the control of mitochondrial Ca2+ metabolism

Probing lipid interactions of plasma membrane proteins: a micropatterning approach

Lipide und Proteine sind keine unabhängigen Bestandteile der Plasmamembran von eukaryotischen Zellen. Vielmehr beeinflussen sie sich gegenseitig in ihrer Anordnung, Dynamik und Funktion. Trotz umfangreicher Studien in den vergangenen Jahrzehnten bleiben viele Fragen zu den fundamentalen Mechanismen, die ihre Interaktion bestimmen, unbeantwortet. In dieser Studie wurde ein Micropatterning Assay optimiert und mit Einzelmolekül-Tracking von verschiedenen Lipiden kombiniert. Dies erlaubte die direkte Messung von Lipid-Protein-Interaktionen in der Plasmamembran lebender Zellen. Für unsere Untersuchungen haben wir zwei Proteine aus verschiedenen Familien ausgewählt: i) CD59, ein Protein, das an der Zellaußenseite der Plasmamembran über einen Glycosylphosphatidylinositol(GPI)-anker gebunden ist und ii) ein palmitoyliertes Transmembranprotein. Während die Modifikation hydrophiler Proteine durch Fettsäuren ihrer Verankerung in der Plasmamembran dient, ist die Funktion der Palmitoylierung für Transmembranproteine noch weitgehend unklar. Eine Hypothese besagt, dass beide posttranslationalen Modifikationen, GPI-Verankerung und Palmitoylierung, die Präferenz von Proteinen für geordnete Membranphasen erhöhen. Ob solche Phasen in lebenden Zellen überhaupt existieren, ist nach wie vor sehr umstritten. In dem hier vorgestellten experimentellen Ansatz wurden die zu untersuchenden Proteine mit Fluorophoren markiert und in definierten Bereichen in der Plasmamembran angereichert. Anschließend wurde die Verteilung und das Diffusionsverhalten von Lipiden und Proteinen in den so generierten Regionen untersucht. Daraus konnten Rückschlüsse auf Lipid-Protein-Wechselwirkungen sowie die lokale Membranumgebung der Proteine gezogen werden. Es zeigte sich, das die Membranviskosität in den mit den ausgewählten Proteinen angereicherten Bereichen unverändert blieb. Die Diffusion der markierten Lipide wurde nur durch sterische Einflüsse der immobilisierten Proteinen beeinflusst. Lipid-spezifische Interaktionen mit Proteinen wurden nicht beobachtet. Experimente mit verschiedenen fluoreszenzmarkierten Lipiden, sowie Cholesterinextraktion, erlaubten weiters, die Bildung von geordneteren Membrandomänen in der Umgebung der Proteine auszuschließen.It is well established that lipids and proteins are not just independent components of the plasma membrane of eukaryotic cells, but that their arrangement, dynamics and function are interdependent. Despite extensive research in the past decades, many questions as to the fundamental underlying mechanisms of how, when and why these species interact with each other, have remained unanswered. In this study, we optimized and used a protein micropatterning assay, and combined it with single-molecule tracking of lipid probes to directly measure lipid-protein interactions in the plasma membrane of living cells. For our studies, we have selected two proteins of interest (POIs) from different families: i) CD59, a protein anchored to the outer leaflet of the plasma membrane via a glycosylphosphatidylinositol(GPI)-anchor, and ii) a truncated version of the palmitoylated transmembrane protein, hemagglutinin (HA). While attachment of fatty acids to soluble proteins clearly serves to facilitate their association with the plasma membrane, the role of palmitoylation for transmembrane proteins is less clear. Both posttranslational modifications, GPI-anchorage and palmitoylation, have been suggested to direct the partitioning of proteins to ordered membrane phases. Whether such phases exist in living cells, however, is still highly debated. In our experimental approach, fluorescently labelled POIs were captured and enriched within well-defined areas in the human plasma membrane, leaving regions depleted of POI, which served as reference areas. From the distribution and diffusion behaviour of lipids and proteins with respect to the POI patterns, we were able to probe lipid-protein interactions as well as the local membrane environment of the POI. We found that the viscosity of the membrane within POI-enriched areas was unchanged. Our lipid probes only experienced steric hindrance by the protein functioning as an obstacle to their diffusion. Moreover, we did not observe any lipid specific lipid-protein interactions. Experiments using different fluorescently labelled lipids as well as cholesterol depletion allowed us to rule out formation of more ordered membrane domains around the proteins.13

Interaction of electromagnetic waves and suprathermal electrons in the near-critical electric field limit

The velocity-space anisotropy of suprathermal electron distributions is a source of free energy that may destabilize plasma waves through a resonant interaction between the waves and the energetic electrons. In this work we use a suprathermal electron distribution appropriate for the case when the accelerating electric field is near-critical and we investigate the frequencies, wave numbers and propagation angles of the most unstable waves using a general dispersion relation. It is shown that if the electric field is sub-critical, the anisotropy is not enough to drive electromagnetic waves unstable, as the Landau damping of the waves overwhelms the drive through the anomalous Doppler resonance. In the case when the electric field is supercritical, two types of electromagnetic waves will be destabilized, the electron-whistler and the extraordinary electron wave. The number of electrons for destabilization of the latter is several orders of magnitude lower than for the electron-whistler wave. Consequently, the threshold for destabilization of the extraordinary electron wave is much lower

Runaway electron dynamics and transport anisotropy due to resonant magnetic perturbations in ITER

In this paper the effect of resonant magnetic perturbations (RMP) on the net radial transport of runaway electrons (RE) is calculated by simulating the RE drift orbits in magnetostatic perturbed fields. Through the transport, RMP influences the time dynamics and preferred loss directions of the REs. The distribution of the field mesh exit points of the runaway electrons become more localised compared to the unperturbed case, since the loss pattern depends on the geometric properties of the RMP configuration such as periodicity or helicity. On the other hand, the loss patterns do not depend on the particle energies and starting positions. The particle radial steps are correlated to the local radial magnetic perturbation component, which makes the transport chaotic, but deterministic

The effect of resonant magnetic perturbations on runaway electron transport in ITER

In this paper the effect of resonant magnetic perturbations (RMPs) on the net radial transport of runaway electrons (REs) is calculated by simulating the RE drift orbits in magnetostatic perturbed fields. Through the transport, RMP influences the time dynamics and preferred loss directions of the REs, which are determined for different magnetic perturbation configurations. The distribution of the field mesh exit points of the REs become more localized compared with the unperturbed case, since the loss pattern depends on the geometric properties of the RMP configuration such as periodicity or helicity. On the other hand, the loss patterns do not depend on the particle energies and starting positions. The particle radial steps are correlated with the local radial magnetic perturbation component, which makes the transport chaotic, but deterministic