Glycogen synthase kinases 3α and 3β in cardiac myocytes: regulation and consequences of their inhibition

Inhibition of glycogen synthase kinase 3β (GSK3β) as a consequence of its phosphorylation by protein kinase B/Akt (PKB/Akt) has been implicated in cardiac myocyte hypertrophy in response to endothelin-1 or phenylephrine. We examined the regulation of GSK3α (which we show to constitute a significant proportion of the myocyte GSK3 pool) and GSK3β in cardiac myocytes. Although endothelin increases phosphorylation of GSK3 and decreases its activity, the response is less than that induced by insulin (which does not promote cardiac myocyte hypertrophy). GSK3 phosphorylation induced by endothelin requires signalling through the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade and not the PKB/Akt pathway, whereas the reverse is true for insulin. Cardiac myocyte hypertrophy involves changes in morphology, and in gene and protein expression. The potent GSK3 inhibitor 1-azakenpaullone increases myocyte area as a consequence of increased cell length whereas phenylephrine increases both length and width. Azakenpaullone or insulin promotes AP1 transcription factor binding to an AP1 consensus oligonucleotide, but this was significantly less than that induced by endothelin and derived principally from increased binding of JunB protein, the expression of which was increased. Azakenpaullone promotes significant changes in gene expression (assessed by Affymetrix microarrays), but the overall response is less than with endothelin and there is little overlap between the genes identified. Thus, although GSK3 may contribute to cardiac myocyte hypertrophy in some respects (and presumably plays an important role in myocyte metabolism), it does not appear to contribute as significantly to the response induced by endothelin as has been maintained

Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

Background: Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results: Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion: The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in this response

Quantum Oscillations in Ferromagnetic (Sb, V)₂Te₃ Topological Insulator Thin Films

An effective way of manipulating 2D surface states in magnetic topological insulators may open a new route for quantum technologies based on the quantum anomalous Hall effect. The doping-dependent evolution of the electronic band structure in the topological insulator Sb2-xVxTe3 (0 <= x <= 0.102) thin films is studied by means of electrical transport. Sb2-xVxTe3 thin films were prepared by molecular beam epitaxy, and Shubnikov-de Hass (SdH) oscillations are observed in both the longitudinal and transverse transport channels. Doping with the 3d element, vanadium, induces long-range ferromagnetic order with enhanced SdH oscillation amplitudes. The doping effect is systematically studied in various films depending on thickness and bottom gate voltage. The angle-dependence of the SdH oscillations reveals their 2D nature, linking them to topological surface states as their origin. Furthermore, it is shown that vanadium doping can efficiently modify the band structure. The tunability by doping and the coexistence of the surface states with ferromagnetism render Sb2-xVxTe3 thin films a promising platform for energy band engineering. In this way, topological quantum states may be manipulated to crossover from quantum Hall effect to quantum anomalous Hall effect, which opens an alternative route for the design of quantum electronics and spintronics

Sustainability in astroparticle physics

The topic of sustainability is becoming increasingly important in research activities in astroparticle physics, both in existing and also in future instrument. At this year\u27s International cosmic ray conference (ICRC 2021) one session was dedicated to this topic. This publication will summarise the findings of this well-attended online session

Hard magnet topological semimetals in XPt₃ compounds with the harmony of Berry curvature

Topological magnetic semimetals, like Co3Sn2S2 and Co2MnGa, display exotic transport properties, such as large intrinsic anomalous (AHE) due to uncompensated Berry curvature. The highly symmetric XPt3 compounds exhibit anti-crossing gapped nodal lines, a driving mechanism in the intrinsic Berry curvature Hall effects. Uniquely, these compounds contain two sets of gapped nodal lines that harmoniously dominate the Berry curvature in this complex multi band system. We calculate a maximum AHE of 1965 S cm-1 in the CrPt3 by first principles electronic structure. We have grown high-quality CrPt3 thin films with perpendicular magnetic anisotropy by magnetron sputtering and measured a robust AHE of 1750 S cm−1 for different sputtering growth conditions. Additionally, the cubic films display an easy magnetic axis along [111] direction. The facile and scalable fabrication of these materials is prime candidates for integration into topological devices

Spin-voltage-driven efficient terahertz spin currents from the magnetic Weyl semimetals Co₂MnGa and Co₂MnAl

Magnetic Weyl semimetals are an emerging material class that combines magnetic order and a topologically non-trivial band structure. Here, we study ultrafast optically driven spin injection from thin films of the magnetic Weyl semimetals Co2MnGa and Co2MnAl into an adjacent Pt layer by means of terahertz emission spectroscopy. We find that (i) Co2MnGa and Co2MnAl are efficient terahertz spin-current generators reaching efficiencies of typical 3d-transition-metal ferromagnets such as Fe. (ii) The relaxation of the spin current provides an estimate of the electron-spin relaxation time of Co2MnGa (165 fs) and Co2MnAl (102 fs), which is comparable to Fe (92 fs). Both observations are consistent with a simple analytical model and highlight the large potential of magnetic Weyl semimetals as spin-current sources in terahertz spintronic devices. Finally, our results provide a strategy to identify magnetic materials that provide maximum spin current amplitudes for a given deposited optical energy density

Nanoscale noncollinear spin textures in thin Films of a D_2d Heusler compound

Magnetic nano-objects, namely antiskyrmions and Bloch skyrmions, have been found to coexist in single-crystalline lamellae formed from bulk crystals of inverse tetragonal Heusler compounds with D2d symmetry. Here evidence is shown for magnetic nano-objects in epitaxial thin films of Mn2RhSn formed by magnetron sputtering. These nano-objects exhibit a wide range of sizes with stability with respect to magnetic field and temperature that is similar to single-crystalline lamellae. However, the nano-objects do not form well-defined arrays, nor is any evidence found for helical spin textures. This is speculated to likely be a consequence of the poorer homogeneity of chemical ordering in the thin films. However, evidence is found for elliptically distorted nano-objects along perpendicular crystallographic directions within the epitaxial films, which is consistent with elliptical Bloch skyrmions observed in single-crystalline lamellae. Thus, these measurements provide strong evidence for the formation of noncollinear spin textures in thin films of Mn2RhSn. Using these films, it is shown that individual nano-objects can be deleted using a local magnetic field from a magnetic tip and collections of nano-objects can be similarly written. These observations suggest a path toward the use of these objects in thin films with D2d symmetry as magnetic memory elements