Unconventional Charge–Spin Conversion in Weyl-Semimetal WTe2

An outstanding feature of topological quantum materials is their novel spin topology in the electronic band structures with an expected large charge-to-spin conversion efficiency. Here, a charge-current-induced spin polarization in the type-II Weyl semimetal candidate WTe2 and efficient spin injection and detection in a graphene channel up to room temperature are reported. Contrary to the conventional spin Hall and Rashba–Edelstein effects, the measurements indicate an unconventional charge-to-spin conversion in WTe2, which is primarily forbidden by the crystal symmetry of the system. Such a large spin polarization can be possible in WTe2 due to a reduced crystal symmetry combined with its large spin Berry curvature, spin–orbit interaction with a novel spin-texture of the Fermi states. A robust and practical method is demonstrated for electrical creation and detection of such a spin polarization using both charge-to-spin conversion and its inverse phenomenon and utilized it for efficient spin injection and detection in the graphene channel up to room temperature. These findings open opportunities for utilizing topological Weyl materials as nonmagnetic spin sources in all-electrical van der Waals spintronic circuits and for low-power and high-performance nonvolatile spintronic technologies

Responsibility, complexity science and education: Dilemmas and uncertain responses

While complexity science is gaining interest among educational theorists, its constructs do not speak to educational responsibility or related core issues in education of power and ethics. Yet certain themes of complexity, as taken up in educational theory, can help unsettle the more controlling and problematic discourses of educational responsibility such as the potential to limit learning and subjectivity or to prescribe social justice. The purpose of this article is to critically examine complexity science against notions of responsibility in terms of implications for education. First, themes of complexity science prominent in contemporary educational writing are explained. Then dilemmas of responsibility in complexity are explored, such as what forms and meanings responsibility can have in a ‘complexified’ perspective of education, how care for others is mobilised, and how desire can be understood. Analyses of ethical action grounded in complexity science are then examined, as well as theories of the ethical subject and participatory responsibility that are congruent with certain tenets of a complexity ontology. Finally, the possibility of an educational vision of responsibility animated by complexity theories is considered, drawing from related writings of Bai, Biesta, Derrida, Levinas and Varela

Intracranial V. cholerae Sialidase Protects against Excitotoxic Neurodegeneration

Converging evidence shows that GD3 ganglioside is a critical effector in a number of apoptotic pathways, and GM1 ganglioside has neuroprotective and noötropic properties. Targeted deletion of GD3 synthase (GD3S) eliminates GD3 and increases GM1 levels. Primary neurons from GD3S−/− mice are resistant to neurotoxicity induced by amyloid-β or hyperhomocysteinemia, and when GD3S is eliminated in the APP/PSEN1 double-transgenic model of Alzheimer's disease the plaque-associated oxidative stress and inflammatory response are absent. To date, no small-molecule inhibitor of GD3S exists. In the present study we used sialidase from Vibrio cholerae (VCS) to produce a brain ganglioside profile that approximates that of GD3S deletion. VCS hydrolyzes GD1a and complex b-series gangliosides to GM1, and the apoptogenic GD3 is degraded. VCS was infused by osmotic minipump into the dorsal third ventricle in mice over a 4-week period. Sensorimotor behaviors, anxiety, and cognition were unaffected in VCS-treated mice. To determine whether VCS was neuroprotective in vivo, we injected kainic acid on the 25th day of infusion to induce status epilepticus. Kainic acid induced a robust lesion of the CA3 hippocampal subfield in aCSF-treated controls. In contrast, all hippocampal regions in VCS-treated mice were largely intact. VCS did not protect against seizures. These results demonstrate that strategic degradation of complex gangliosides and GD3 can be used to achieve neuroprotection without adversely affecting behavior

In silico design of novel probes for the atypical opioid receptor MRGPRX2

The primate-exclusive MRGPRX2 G protein-coupled receptor (GPCR) has been suggested to modulate pain and itch. Despite putative peptide and small molecule MRGPRX2 agonists, selective nanomolar potency probes have not yet been reported. To identify a MRGPRX2 probe, we first screened 5,695 small molecules and found many opioid compounds activated MRGPRX2, including (−)- and (+)-morphine, hydrocodone, sinomenine, dextromethorphan and the prodynorphin-derived peptides, dynorphin A, dynorphin B, and α- and β-neoendorphin. We used these to select for mutagenesis-validated homology models and docked almost 4 million small molecules. From this docking, we predicted ZINC-3573, which represents a potent MRGPRX2-selective agonist, showing little activity against 315 other GPCRs and 97 representative kinases, and an essentially inactive enantiomer. ZINC-3573 activates endogenous MRGPRX2 in a human mast cell line inducing degranulation and calcium release. MRGPRX2 is a unique atypical opioid-like receptor important for modulating mast cell degranulation, which can now be specifically modulated with ZINC-3573

In silico design of novel probes for the atypical opioid receptor MRGPRX2.

The primate-exclusive MRGPRX2 G protein-coupled receptor (GPCR) has been suggested to modulate pain and itch. Despite putative peptide and small-molecule MRGPRX2 agonists, selective nanomolar-potency probes have not yet been reported. To identify a MRGPRX2 probe, we first screened 5,695 small molecules and found that many opioid compounds activated MRGPRX2, including (-)- and (+)-morphine, hydrocodone, sinomenine, dextromethorphan, and the prodynorphin-derived peptides dynorphin A, dynorphin B, and α- and β-neoendorphin. We used these to select for mutagenesis-validated homology models and docked almost 4 million small molecules. From this docking, we predicted ZINC-3573-a potent MRGPRX2-selective agonist, showing little activity against 315 other GPCRs and 97 representative kinases-along with an essentially inactive enantiomer. ZINC-3573 activates endogenous MRGPRX2 in a human mast cell line, inducing degranulation and calcium release. MRGPRX2 is a unique atypical opioid-like receptor important for modulating mast cell degranulation, which can now be specifically modulated with ZINC-3573