Entry into the nuclear pore complex is controlled by a cytoplasmic exclusion zone containing dynamic GLFG-repeat nucleoporin domains

Nuclear pore complexes (NPCs) mediate nucleocytoplasmic movement. The central channel contains proteins with phenylalanine-glycine (FG) repeats, or variations (GLFG, glycine-leucine-phenylalanine-glycine). These are ‘intrinsically disordered’ and often represent weak interaction sites that become ordered upon interaction. We investigated this possibility during nuclear transport. Using electron microscopy of S. cerevisiae, we show that NPC cytoplasmic filaments form a dome-shaped structure enclosing GLFG domains. GLFG domains extend out of this structure and are part of an ‘exclusion zone’ that might act as a partial barrier to entry of transport-inert proteins. The anchor domain of a GLFG nucleoporin locates exclusively to the central channel. By contrast, the localisation of the GLFG domains varied between NPCs and could be cytoplasmic, central or nucleoplasmic and could stretch up to 80 nm. These results suggest a dynamic exchange between ordered and disordered states. In contrast to diffusion through the NPC, transport cargoes passed through the exclusion zone and accumulated near the central plane. We also show that movement of cargo through the NPC is accompanied by relocation of GLFG domains, suggesting that binding, restructuring and movement of these domains could be part of the translocation mechanism

Spin-orbit coupling in bulk GaAs

We study the spin-orbit coupling in the whole Brillouin zone for GaAs using both the $sp^3s^{\ast}d^5$ and $sp^3s^{\ast}$ nearest-neighbor tight-binding models. In the $\Gamma$-valley, the spin splitting obtained is in good agreement with experimental data. We then further explicitly present the coefficients of the spin splitting in GaAs $L$ and $X$ valleys. These results are important to the realization of spintronic device and the investigation of spin dynamics far away from equilibrium.Comment: 8 pages, 3 figures, Physica E, in pres

A Bayesian Approach to Calibrating Period-Luminosity Relations of RR Lyrae Stars in the Mid-Infrared

A Bayesian approach to calibrating period-luminosity (PL) relations has substantial benefits over generic least-squares fits. In particular, the Bayesian approach takes into account the full prior distribution of the model parameters, such as the a priori distances, and refits these parameters as part of the process of settling on the most highly-constrained final fit. Additionally, the Bayesian approach can naturally ingest data from multiple wavebands and simultaneously fit the parameters of PL relations for each waveband in a procedure that constrains the parameter posterior distributions so as to minimize the scatter of the final fits appropriately in all wavebands. Here we describe the generalized approach to Bayesian model fitting and then specialize to a detailed description of applying Bayesian linear model fitting to the mid-infrared PL relations of RR Lyrae variable stars. For this example application we quantify the improvement afforded by using a Bayesian model fit. We also compare distances previously predicted in our example application to recently published parallax distances measured with the Hubble Space Telescope and find their agreement to be a vindication of our methodology. Our intent with this article is to spread awareness of the benefits and applicability of this Bayesian approach and encourage future PL relation investigations to consider employing this powerful analysis method.Comment: 6 pages, 1 figure. Accepted for publication in Astrophysics & Space Science. Following a presentation at the conference The Fundamental Cosmic Distance Scale: State of the Art and the Gaia Perspective, Naples, May 201

Excited Baryons in Lattice QCD

We present first results for the masses of positive and negative parity excited baryons calculated in lattice QCD using an O(a^2)-improved gluon action and a fat-link irrelevant clover (FLIC) fermion action in which only the irrelevant operators are constructed with APE-smeared links. The results are in agreement with earlier calculations of N^* resonances using improved actions and exhibit a clear mass splitting between the nucleon and its chiral partner. An correlation matrix analysis reveals two low-lying J^P=(1/2)^- states with a small mass splitting. The study of different Lambda interpolating fields suggests a similar splitting between the lowest two Lambda1/2^- octet states. However, the empirical mass suppression of the Lambda^*(1405) is not evident in these quenched QCD simulations, suggesting a potentially important role for the meson cloud of the Lambda^*(1405) and/or a need for more exotic interpolating fields.Comment: Correlation matrix analysis performed. Increased to 400 configurations. 22 pages, 13 figures, 15 table

Mitotic phosphorylation by NEK6 and NEK7 reduces microtubule affinity of EML4 to promote chromosome congression

EML4 is a microtubule-associated protein that promotes microtubule stability. We investigated its regulation across the cell cycle and found that EML4 was distributed as punctate foci along the microtubule lattice in interphase but exhibited reduced association with spindle microtubules in mitosis. Microtubule sedimentation and cryo-electron microscopy with 3D reconstruction revealed that the basic N-terminal domain of EML4 mediated its binding to the acidic C-terminal tails of α- and β-tubulin on the microtubule surface. The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stability and interfered with chromosome congression. Meanwhile, constitutive activation of NEK6 or NEK7 reduced EML4 association with interphase microtubules. Together, these data support a model in which NEK6- and NEK7- dependent phosphorylation promotes dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression

EML4-ALK V3 oncogenic fusion proteins promote microtubule stabilization and accelerated migration through NEK9 and NEK7

EML4-ALK is an oncogenic fusion present in ∼5% non-small cell lung cancers. However, alternative breakpoints in the EML4 gene lead to distinct variants with different patient outcomes. Here, we show in cell models that EML4-ALK variant 3 (V3), which is linked to accelerated metastatic spread, causes microtubule stabilization, formation of extended cytoplasmic protrusions and increased cell migration. It also recruits the NEK9 and NEK7 kinase to microtubules via the N-terminal EML4 microtubule-binding region. Overexpression of wild-type EML4 as well as constitutive activation of NEK9 also perturb cell morphology and accelerate migration in a microtubule-dependent manner that requires the downstream kinase NEK7 but not ALK activity. Strikingly, elevated NEK9 expression is associated with reduced progression-free survival in EML4-ALK patients. Hence, we propose that EML4-ALK V3 promotes microtubule stabilization through NEK9 and NEK7 leading to increased cell migration. This represents a novel actionable pathway that could drive metastatic disease progression in EML4-ALK lung cancer

Orbital precession modulates interannual rainfall variability, as recorded in an Early Pleistocene speleothem

Interannual variability of African rainfall impacts local and global communities, but its past behavior and response in future climate projections are poorly understood. This is primarily due to short instrumental records and a lack of long high-resolution palaeoclimate proxy records. Here we present an annually resolved 91,000 year Early Pleistocene record of hydroclimate from the early homininbearing Makapansgat Valley, South Africa. Changes in speleothem annual band thickness are dominated by precession over four consecutive orbital cycles with strong millennial-scale periodicity. The frequency of interannual variability (2.0–6.5 yr oscillations) does not change systematically, yet its amplitude is modulated by the orbital forcing. These long-term characteristics of interannual variability are reproduced with transient climate model simulations of water balance for South Africa from the Late Pleistocene to Recent. Based on these results, we suggest that the frequency of interannual variations in southern African rainfall is likely to be stable under anthropogenic warming, but that the size of year-to-year variations may increase. We see an orbitally forced increase in the amplitude of interannual climate variability between 1.8 Ma and 1.7 Ma coincident with the first evidence for the Acheulean stone tool technology

Spin dynamics in semiconductors

This article reviews the current status of spin dynamics in semiconductors which has achieved a lot of progress in the past years due to the fast growing field of semiconductor spintronics. The primary focus is the theoretical and experimental developments of spin relaxation and dephasing in both spin precession in time domain and spin diffusion and transport in spacial domain. A fully microscopic many-body investigation on spin dynamics based on the kinetic spin Bloch equation approach is reviewed comprehensively.Comment: a review article with 193 pages and 1103 references. To be published in Physics Reports