Polarised cell migration is required for various cell behaviours and functions. Actin and microtubules are coupled structurally and distributed asymmetrically along the front-rear axis of migrating cells. CLIP-associating proteins (CLASPs) accumulate near the ends of microtubules at the front of migrating cells to control microtubule dynamics and cytoskeletal coupling. Regional inhibition of GSK-3β is responsible for this asymmetric distribution of CLASPs. However, it is not known how GSK-3β regulates the activity of CLASPs for linkage between actin and microtubules. Here we identified IQGAP1, an actin-binding protein, as a novel CLASP-binding protein. GSK-3β directly phosphorylates CLASP2 at Ser533 and Ser537 within the region responsible for the IQGAP1 binding. Phosphorylation of CLASP2 results in the dissociation of CLASP2 from IQGAP1, EB1 and microtubules. At the leading edges of migrating fibroblasts, CLASP2 near microtubule ends partially colocalises with IQGAP1. Expression of active GSK-3β abrogates the distribution of CLASP2 on microtubules, but not that of a nonphosphorylatable CLASP2 mutant. The phosphorylated CLASP2 does not accumulate near the ends of microtubules at the leading edges. Thus, phosphorylation of CLASP2 by GSK-3β appears to control the regional linkage of microtubules to actin filaments through IQGAP1 for cell migration.

Rac1 and Cdc42, members of the Rho family GTPases, control diverse cellular processes such as cell migration and morphogenesis through their effectors. Among the effectors, IQGAP1 plays pivotal roles in the establishment of cytoskeletal architecture and intercellular adhesions in various cells. However, its roles remain to be clarified, especially in neuronal cells. We have identified IQGAP3 as a novel member of the IQGAP family, which is highly expressed in brain. We found that IQGAP3, an effector of Rac1 and Cdc42, associates directly with actin filaments and accumulates asymmetrically at the distal region of axons in hippocampal neurons. The depletion of IQGAP3 impairs neurite or axon outgrowth in neuronal cells with the disorganized cytoskeleton, but depletion of IQGAP1 does not. Furthermore, IQGAP3 is indispensable for Rac1/Cdc42-promoted neurite outgrowth in PC12 cells. Taken together, these results indicate that IQGAP3 can link the activation of Rac1 and Cdc42 with the cytoskeletal architectures during neuronal morphogenesis.

The addition of artificial pinning centers has led to an impressive increase in the critical current density (Jc) of superconductors, enabling record-breaking all-superconducting magnets and other applications. The Jc of superconductors has reached ~0.2–0.3 Jd, where Jd is the depairing current density, and the numerical factor depends on the pinning optimization. By modifying λ and/or ξ, the penetration depth and coherence length, respectively, we can increase Jd. For (Y0.77Gd0.23)Ba2Cu3Oy ((Y,Gd)123), we can achieve this by controlling the carrier density, which is related to λ and ξ. We can also tune λ and ξ by controlling the chemical pressure in Fe-based superconductors, i.e., BaFe2(As1−xPx)2 films. The variation in λ and ξ leads to an intrinsic improvement in Jc via Jd, allowing extremely high values of Jc of 130 MA/cm2 and 8.0 MA/cm2 at 4.2 K, consistent with an enhancement in Jd of a factor of 2 for both incoherent nanoparticle-doped (Y,Gd)123 coated conductors (CCs) and BaFe2(As1−xPx)2 films, showing that this new material design is useful for achieving high critical current densities in a wide array of superconductors. The remarkably high vortex-pinning force in combination with this thermodynamic and pinning optimization route for the (Y,Gd)123 CCs reached ~3.17 TN/m3 at 4.2 K and 18 T (H||c), the highest values ever reported for any superconductor.

The effectiveness of calcium antagonists on a chronic cerebral vasospasm after an SAH is still under debate. Calcium channel blockers such as nimodipine, nifedipine etc. can dilate spastic arteries by intrathecal administration, but not by systemic (iv or po) use. HA 1077 is a novel and potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits 1. calcium ionophore A 23187 induced contraction in arterial strips and 2. phenylephrine induced contraction in calcium free media, suggesting that its site of action is in the intracellular space. HA 1077 is water soluble and relatively stable in light. In the present study, the efficacy of HA 1077 was evaluated on dogs by using the spiral arterial strips in vitro and by angiography in vivo. In the arterial strips from the control dogs, a 50% relaxation of KCl (15 mM) induced contraction was obtained by a 10(-6) M HA 1077 for the "intracranial" basilar and middle cerebral arteries, while a 10(-5) M was needed to obtain the same effect for the "extracranial" common carotid and vertebral arteries, indicating that HA 1077 is more effective for the intracranial arteries. A vasospasm was produced by the "two haemorrhage" model of Varsos et al. The average angiographic diameter of the basilar artery was reduced to 60% of the control on SAH day 7. Intravenous infusion of HA 1077 (0.5-3 mg/kg/30 min) significantly dilated the spastic basilar artery (up to 20-30%), for over 2 hours. A fall in the systemic BP remained less than 20% during this time.(ABSTRACT TRUNCATED AT 250 WORDS)

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The high upper critical field and low anisotropy of the 122-type iron-based superconductor BaFe2As2 makes it promising for use in superconducting high field magnets. However, its critical current density (J c) in high magnetic fields needs to be further improved. Here we show that for the film prepared by pulsed laser deposition method by controlling the deposition parameters (higher substrate temperature and lower growth rate), the crystallinity of BaFe2(As0.66P0.33)2 (Ba122:P) matrix is improved while maintaining a high density of incoherent BaZrO3 (BZO) nanoparticles (NPs) which together lead to significantly increased self field J c. Our Ba122:P nanocomposite films also exhibit increased in-field J c, reduced angular anisotropy of J c and reduced detrimental effects of thermal fluctuations (creep rate) over a wide range of temperatures and magnetic field strength. The BZO NP doped Ba122:P films show high in-field J c over 2.1 MA cm−2 even at 4 K and 9 T (μ 0 H∣∣c), which is significantly higher than that of standard Ba122:P films and conventional alloy superconducting wires. To understand the contribution of the various pinning centers, we applied a simple model, which was developed for cuprates, to Ba122:P film with all the parameters used derived by fitting to a limited set of experimental data (no free parameters) such that temperature, angle and field properties at other experimental conditions are then calculated. This simple model fits very well to the experimental results in these two very different material systems. We discuss the effectiveness of natural defect and BZO NPs on the ratio of J c to the depairing current density. The superconducting properties for 122-type iron-based superconductors obtained through this work are considered promising for high-field applications.

This paper presents a promising approach to reduce the quantity of Pt required in cathodes for high‐temperature proton exchange membrane (PEM) fuel cells. Based on preliminary experiments, thermally stable Si0.97Al0.03C and Sn0.95In0.05P2O7 were selected as promoter and ionomer, respectively. Si0.97Al0.03C particles (∼40 nm) and Sn0.95In0.05P2O7 particles (∼45 nm) were successfully produced on a carbon support. Pt particles (∼9 nm) were selectively impregnated in the vicinity of the ionomer. Polarisation measurements revealed that the Pt‐Sn0.95In0.05P2O7‐Si0.97Al0.03C/C cathode exhibited much higher oxygen reduction reaction (ORR) activity than that observed for a pure Pt/C cathode, due to the enhanced dissociative oxygen adsorption on the Si0.97Al0.03C particles and the increased number of reaction sites for the ORR provided by the Sn0.95In0.05P2O7 particles. Fuel cell operation tests demonstrated that a Pt‐Sn0.95In0.05P2O7‐Si0.97Al0.03C/C cathode with a low Pt loading of 0.1 mg cm–2 provides better cell performance than a Pt/C cathode with a Pt loading of 1.0 mg cm–2.