335 research outputs found
Weak-field induced nonmagnetic state in a Co-based honeycomb
Layered honeycomb magnets are of interest as potential realizations of the
Kitaev quantum spin liquid (KQSL), a quantum state with long-range spin
entanglement and an exactly solvable Hamiltonian. Conventional magnetically
ordered states are present for all currently known candidate materials,
however, because non-Kitaev terms in the Hamiltonians obscure the Kitaev
physics. Current experimental studies of the KQSL are focused on 4d- or
5d-transition-metal-based honeycombs, in which strong spin-orbit coupling can
be expected, yielding Kitaev interaction that dominate in an applied magnetic
field. In contrast, for 3d-based layered honeycomb magnets, spin orbit coupling
is weak and thus Kitaev-physics should be substantially less accessible. Here
we report our studies on BaCo2(AsO4)2, for which we find that the magnetic
order associated with the non-Kitaev interactions can be fully suppressed by a
relatively low magnetic field, yielding a non-magnetic material and implying
the presence of strong magnetic frustration and weak non-Kitaev interactions
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Nanomolar-potency 'co-potentiator' therapy for cystic fibrosis caused by a defined subset of minimal function CFTR mutants.
Available CFTR modulators provide no therapeutic benefit for cystic fibrosis (CF) caused by many loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, including N1303K. We previously introduced the concept of 'co-potentiators' (combination-potentiators) to rescue CFTR function in some minimal function CFTR mutants. Herein, a screen of ~120,000 drug-like synthetic small molecules identified active co-potentiators of pyrazoloquinoline, piperidine-pyridoindole, tetrahydroquinoline and phenylazepine classes, with EC50 down to ~300 nM following initial structure-activity studies. Increased CFTR chloride conductance by up to 8-fold was observed when a co-potentiator (termed 'Class II potentiator') was used with a classical potentiator ('Class I potentiator') such as VX-770 or GLPG1837. To investigate the range of CFTR mutations benefitted by co-potentiators, 14 CF-associated CFTR mutations were studied in transfected cell models. Co-potentiator efficacy was found for CFTR missense, deletion and nonsense mutations in nucleotide binding domain-2 (NBD2), including W1282X, N1303K, c.3700A > G and Q1313X (with corrector for some mutations). In contrast, CFTR mutations G85E, R334W, R347P, V520F, R560T, A561E, M1101K and R1162X showed no co-potentiator activity, even with corrector. Co-potentiator efficacy was confirmed in primary human bronchial epithelial cell cultures generated from a N1303K homozygous CF subject. The Class II potentiators identified here may have clinical benefit for CF caused by mutations in the NBD2 domain of CFTR
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Bioactive Thymosin Alpha-1 Does Not Influence F508del-CFTR Maturation and Activity.
Deletion of phenylalanine 508 (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is the most frequent mutation causing cystic fibrosis (CF). F508del-CFTR is misfolded and prematurely degraded. Recently thymosin a-1 (Tα-1) was proposed as a single molecule-based therapy for CF, improving both F508del-CFTR maturation and function by restoring defective autophagy. However, three independent laboratories failed to reproduce these results. Lack of reproducibility has been ascribed by the authors of the original paper to the use of DMSO and to improper handling. Here, we address these potential issues by demonstrating that Tα-1 changes induced by DMSO are fully reversible and that Tα-1 peptides prepared from different stock solutions have equivalent biological activity. Considering the negative results here reported, six independent laboratories failed to demonstrate F508del-CFTR correction by Tα-1. This study also calls into question the autophagy modulator cysteamine, since no rescue of mutant CFTR function was detected following treatment with cysteamine, while deleterious effects were observed when bronchial epithelia were exposed to cysteamine plus the antioxidant food supplement EGCG. Although these studies do not exclude the possibility of beneficial immunomodulatory effects of thymosin α-1, they do not support its utility as a corrector of F508del-CFTR
High mobility in a van der Waals layered antiferromagnetic metal
Magnetic van der Waals (vdW) materials have been heavily pursued for
fundamental physics as well as for device design. Despite the rapid advances,
so far magnetic vdW materials are mainly insulating or semiconducting, and none
of them possesses a high electronic mobility - a property that is rare in
layered vdW materials in general. The realization of a magnetic high-mobility
vdW material would open the possibility for novel magnetic twistronic or
spintronic devices. Here we report very high carrier mobility in the layered
vdW antiferromagnet GdTe3. The electron mobility is beyond 60,000 cm2 V-1 s-1,
which is the highest among all known layered magnetic materials, to the best of
our knowledge. Among all known vdW materials, the mobility of bulk GdTe3 is
comparable to that of black phosphorus, and is only surpassed by graphite. By
mechanical exfoliation, we further demonstrate that GdTe3 can be exfoliated to
ultrathin flakes of three monolayers, and that the magnetic order and
relatively high mobility is retained in approximately 20-nm-thin flakes
Exploration of a novel Type II 1D-ZnO nanorods/BiVO 4 heterojunction photocatalyst for water depollution
Abstract(#br)In this study, we reported on the successful fabrication of a novel heterojunction photocatalyst (in particulate system) with a Type II band alignment between 1D-ZnO nanorods and BiVO 4 nanocrystals. Pristine 1D-ZnO nanorods and BiVO 4 nanocrystals were first fabricated through hydrothermal reaction followed by heterojunction formation via the wet chemical reaction. The 1D-ZnO/ x BiVO 4 heterojunction photocatalyst (
Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF
Colossal negative magnetoresistance in the complex charge density wave regime of an antiferromagnetic Dirac semimetal
Colossal magnetoresistance (MR) is a well-known phenomenon, notably observed
in hole-doped ferromagnetic manganites. It remains a major research topic due
to its potential in technological applications. Though topological semimetals
also show large MR, its origin and nature are completely different. Here, we
show that in the highly electron doped region, the Dirac semimetal CeSbTe
demonstrates similar properties as the manganites. CeSbTe
hosts multiple charge density wave (CDW) modulation-vectors and has a complex
magnetic phase diagram. We confirm that this compound is an antiferromagnetic
Dirac semimetal. Despite having a metallic Fermi surface, the electronic
transport properties are semiconductor-like and deviate from known theoretical
models. An external magnetic field induces a semiconductor-metal-like
transition, which results in a colossal negative MR. Moreover, signatures of
the coupling between the CDW and a spin modulation are observed in resistivity.
This spin modulation also produces a giant anomalous Hall response.Comment: 11 pages, 13 figure
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