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Sökning: WFRF:(Kuespert J.)

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1.
  • Wang, Qisi, et al. (författare)
  • Uniaxial pressure induced stripe order rotation in La1.88Sr0.12CuO4
  • 2022
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Static stripe order is detrimental to superconductivity. Yet, it has been proposed that transverse stripe fluctuations may enhance the inter-stripe Josephson coupling and thus promote superconductivity. Direct experimental studies of stripe dynamics, however, remain difficult. From a strong-coupling perspective, transverse stripe fluctuations are realized in the form of dynamic "kinks"-sideways shifting stripe sections. Here, we show how modest uniaxial pressure tuning reorganizes directional kink alignment. Our starting point is La1.88Sr0.12CuO4 where transverse kink ordering results in a rotation of stripe order away from the crystal axis. Application of mild uniaxial pressure changes the ordering pattern and pins the stripe order to the crystal axis. This reordering occurs at a much weaker pressure than that to detwin the stripe domains and suggests a rather weak transverse stripe stiffness. Weak spatial stiffness and transverse quantum fluctuations are likely key prerequisites for stripes to coexist with superconductivity. Transverse stripe order fluctuations may promote superconductivity, but experimental verifications remain difficult. Here, the authors report that a mild uniaxial pressure changes the ordering pattern and pins the stripe order to the crystal axis in La1.88Sr0.12CuO4.
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2.
  • Peters, S., et al. (författare)
  • Reconditioning the Neurogenic Niche of Adult Non-human Primates by Antisense Oligonucleotide-Mediated Attenuation of TGFβ Signaling
  • 2021
  • Ingår i: Neurotherapeutics. - : Springer Nature. - 1933-7213 .- 1878-7479. ; 18:3, s. 1963-1979
  • Tidskriftsartikel (refereegranskat)abstract
    • Adult neurogenesis is a target for brain rejuvenation as well as regeneration in aging and disease. Numerous approaches showed efficacy to elevate neurogenesis in rodents, yet translation into therapies has not been achieved. Here, we introduce a novel human TGFβ-RII (Transforming Growth Factor—Receptor Type II) specific LNA-antisense oligonucleotide (“locked nucleotide acid”—“NVP-13”), which reduces TGFβ-RII expression and downstream receptor signaling in human neuronal precursor cells (ReNcell CX® cells) in vitro. After we injected cynomolgus non-human primates repeatedly i.th. with NVP-13 in a preclinical regulatory 13-week GLP-toxicity program, we could specifically downregulate TGFβ-RII mRNA and protein in vivo. Subsequently, we observed a dose-dependent upregulation of the neurogenic niche activity within the hippocampus and subventricular zone: human neural progenitor cells showed significantly (up to threefold over control) enhanced differentiation and cell numbers. NVP-13 treatment modulated canonical and non-canonical TGFβ pathways, such as MAPK and PI3K, as well as key transcription factors and epigenetic factors involved in stem cell maintenance, such as MEF2A and pFoxO3. The latter are also dysregulated in clinical neurodegeneration, such as amyotrophic lateral sclerosis. Here, we provide for the first time in vitro and in vivo evidence for a novel translatable approach to treat neurodegenerative disorders by modulating neurogenesis.
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