The RECEPTOR-LIKE PROTEIN53 immune complex associates with LLG1 to positively regulate plant immunity.

Pattern recognition receptors (PRRs) sense ligands in pattern-triggered immunity (PTI). Plant PRRs include numerous receptor-like proteins (RLPs), but many RLPs remain functionally uncharacterized. Here, we examine an Arabidopsis thaliana RLP, RLP53, which positively regulates immune signaling. Our forward genetic screen for suppressors of enhanced disease resistance1 (edr1) identified a point mutation in RLP53 that fully suppresses disease resistance and mildew-induced cell death in edr1 mutants. The rlp53 mutants showed enhanced susceptibility to virulent pathogens, including fungi, oomycetes, and bacteria, indicating that RLP53 is important for plant immunity. The ectodomain of RLP53 contains leucine-rich repeat (LRR) motifs. RLP53 constitutively associates with the LRR receptor-like kinase SUPPRESSOR OF BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE (BAK1)-INTERACTING RECEPTOR KINASE1 (SOBIR1) and interacts with the co-receptor BAK1 in a pathogen-induced manner. The double mutation sobir1-12 bak1-5 suppresses edr1-mediated disease resistance, suggesting that EDR1 negatively regulates PTI modulated by the RLP53-SOBIR1-BAK1 complex. Moreover, the glycosylphosphatidylinositol (GPI)-anchored protein LORELEI-LIKE GPI-ANCHORED PROTEIN1 (LLG1) interacts with RLP53 and mediates RLP53 accumulation in the plasma membrane. We thus uncovered the role of a novel RLP and its associated immune complex in plant defense responses and revealed a potential new mechanism underlying regulation of RLP immune function by a GPI-anchored protein.

Atomistic theory of thermally activated magnetization processes in Nd2Fe14B permanent magnet.

To study the temperature dependence of magnetic properties of permanent magnets, methods of treating the thermal fluctuation causing the thermal activation phenomena must be established. To study finite-temperature properties quantitatively, we need atomistic energy information to calculate the canonical distribution. In the present review, we report our recent studies on the thermal properties of the Nd2Fe14B magnet and the methods of studying them. We first propose an atomistic Hamiltonian and show various thermodynamic properties, for example, the temperature dependences of the magnetization showing a spin reorientation transition, the magnetic anisotropy energy, the domain wall profiles, the anisotropy of the exchange stiffness constant, and the spectrum of ferromagnetic resonance. The effects of the dipole-dipole interaction (DDI) in large grains are also presented. In addition to these equilibrium properties, the temperature dependence of the coercivity of a single grain was studied using the stochastic Landau-Lifshitz-Gilbert equation and also by the analysis of the free energy landscape, which was obtained by Monte Carlo simulation. The upper limit of coercivity at room temperature was found to be about 3 T at room temperature. The coercivity of a polycrystalline magnet, that is, an ensemble of interactinve grains, is expected to be reduced further by the effects of the grain boundary phase, which is also studied. Surface nucleation is a key ingredient in the domain wall depinning process. Finally, we study the effect of DDI among grains and also discuss the distribution of properties of grains from the viewpoint of first-order reversal curve.

Arabidopsis glycosylphosphatidylinositol-anchored protein LLG1 associates with and modulates FLS2 to regulate innate immunity.

Plants detect and respond to pathogen invasion with membrane-localized pattern recognition receptors (PRRs), which recognize pathogen-associated molecular patterns (PAMPs) and activate downstream immune responses. Here we report that Arabidopsis thaliana LORELEI-LIKE GPI-ANCHORED PROTEIN 1 (LLG1), a coreceptor of the receptor-like kinase FERONIA, regulates PRR signaling. In a forward genetic screen for suppressors of enhanced disease resistance 1 (edr1), we identified the point mutation llg1-3, which suppresses edr1 disease resistance but does not affect plant growth and development. The llg1 mutants show enhanced susceptibility to various virulent pathogens, indicating that LLG1 has an important role in plant immunity. LLG1 constitutively associates with the PAMP receptor FLAGELLIN SENSING 2 (FLS2) and the elongation factor-Tu receptor, and forms a complex with BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR KINASE 1 in a ligand-dependent manner, indicating that LLG1 functions as a key component of PAMP-recognition immune complexes. Moreover, LLG1 contributes to accumulation and ligand-induced degradation of FLS2, and is required for downstream innate immunity responses, including ligand-induced phosphorylation of BOTRYTIS-INDUCED KINASE 1 and production of reactive oxygen species. Taken together, our findings reveal that LLG1 associates with PAMP receptors and modulates their function to regulate disease responses. As LLG1 functions as a coreceptor of FERONIA and plays central roles in plant growth and development, our findings indicate that LLG1 participates in separate pathways, and may suggest a potential connection between development and innate immunity in plants.

Magnetic Field-Optimized Paramagnetic Nanoprobe for T2/T1 Switchable Histopathological-Level MRI.

Traditional magnetic resonance imaging (MRI) contrast agents (CAs) are a type of "always on" system that accelerates proton relaxation regardless of their enrichment region. This "always on" feature leads to a decrease in signal differences between lesions and normal tissues, hampering their applications in accurate and early diagnosis. Herein, we report a strategy to fabricate glutathione (GSH)-responsive one-dimensional (1-D) manganese oxide nanoparticles (MONPs) with improved T2 relaxivities and achieve effective T2/T1 switchable MRI imaging of tumors. Compared to traditional contrast agents with high saturation magnetization to enhance T2 relaxivities, 1-D MONPs with weak Ms effectively increase the inhomogeneity of the local magnetic field and exhibit obvious T2 contrast. The inhomogeneity of the local magnetic field of 1-D MONPs is highly dependent on their number of primary particles and surface roughness according to Landau-Lifshitz-Gilbert simulations and thus eventually determines their T2 relaxivities. Furthermore, the GSH responsiveness ensures 1-D MONPs with sensitive switching from the T2 to T1 mode in vitro and subcutaneous tumors to clearly delineate the boundary of glioma and metastasis margins, achieving precise histopathological-level MRI. This study provides a strategy to improve T2 relaxivity of magnetic nanoparticles and construct switchable MRI CAs, offering high tumor-to-normal tissue contrast signal for early and accurate diagnosis.

Combining micromagnetism and magnetostatic Maxwell equations for multiscale magnetic simulations.

Magnetostatic Maxwell equations and the Landau-Lifshitz-Gilbert (LLG) equation are combined to a multiscale method, which allows to extend the problem size of traditional micromagnetic simulations. By means of magnetostatic Maxwell equations macroscopic regions can be handled in an averaged and stationary sense, whereas the LLG allows to accurately describe domain formation as well as magnetization dynamics in some microscopic subregions. The two regions are coupled by means of their strayfield and the combined system is solved by an optimized time integration scheme.

Tunability of spin-wave spectra in a 2D triangular shaped magnonic fractals.

Reprogramming the structure of the magnonic bands during their operation is important for controlling spin waves in magnonic devices. Here, we report the tunability of the spin-wave spectra for a triangular shaped deterministic magnonic fractal, which is known as Sierpinski triangle by solving the Landau-Lifshitz-Gilbert equation using a micromagnetic simulations. The spin-wave dynamics change significantly with the variation of iteration number. A wide frequency gap is observed for a structure with an iteration number exceeding some value and a plenty of mini-frequency bandgaps at structures with high iteration number. The frequency gap could be controlled by varying the strength of the magnetic field. A sixfold symmetry in the frequency gap is observed with the variation of the azimuthal angle of the external magnetic field. The spatial distributions of the spin-wave modes allow to identify the bands surrounding the gap. The observations are important for the application of magnetic fractals as a reconfigurable aperiodic magnonic crystals.

The role of interfacial intermixing on HAMR dynamics in bilayer media.

We use an atomistic spin model to simulate FePt-based bilayers for heat assisted magnetic recording (HAMR) devices and investigate the effect of various degrees intermixing that might arise throughout the fabrication, growth and annealing processes, as well as different interlayer exchange couplings, on HAMR magnetisation dynamics. Intermixing can impact the device functionality, but interestingly does not deteriorate the properties of the system. Our results suggest that modest intermixing can prove beneficial and yield an improvement in the magnetisation dynamics for HAMR processes, also relaxing the requirement for weak exchange coupling between the layers. Therefore, we propose that a certain intermixing across the interface could be engineered in the fabrication process to improve HAMR technology further.

Fast magnetization reversal of a magnetic nanoparticle induced by cosine chirp microwave field pulse.

We investigate the magnetization reversal of single-domain magnetic nanoparticle driven by the circularly polarized cosine chirp microwave pulse (CCMP). The numerical findings, based on the Landau-Lifshitz-Gilbert equation, reveal that the CCMP is by itself capable of driving fast and energy-efficient magnetization reversal. The microwave field amplitude and initial frequency required by a CCMP are much smaller than that of the linear down-chirp microwave pulse. This is achieved as the frequency change of the CCMP closely matches the frequency change of the magnetization precession which leads to an efficient stimulated microwave energy absorption (emission) by (from) the magnetic particle before (after) it crosses over the energy barrier. We further find that the enhancement of easy-plane shape anisotropy significantly reduces the required microwave amplitude and the initial frequency of CCMP. We also find that there is an optimal Gilbert damping for fast magnetization reversal. These findings may provide a pathway to realize the fast and low-cost memory device.

Factors influencing estimates of coordinate error for molecular replacement.

Good prior estimates of the effective root-mean-square deviation (r.m.s.d.) between the atomic coordinates of the model and the target optimize the signal in molecular replacement, thereby increasing the success rate in difficult cases. Previous studies using protein structures solved by X-ray crystallography as models showed that optimal error estimates (refined after structure solution) were correlated with the sequence identity between the model and target, and with the number of residues in the model. Here, this work has been extended to find additional correlations between parameters of the model and the target and hence improved prior estimates of the coordinate error. Using a graph database, a curated set of 6030 molecular-replacement calculations using models that had been solved by X-ray crystallography was analysed to consider about 120 model and target parameters. Improved estimates were achieved by replacing the sequence identity with the Gonnet score for sequence similarity, as well as by considering the resolution of the target structure and the MolProbity score of the model. This approach was extended by analysing 12 610 additional molecular-replacement calculations where the model was determined by NMR. The median r.m.s.d. between pairs of models in an ensemble was found to be correlated with the estimated r.m.s.d. to the target. For models solved by NMR, the overall coordinate error estimates were larger than for structures determined by X-ray crystallography, and were more highly correlated with the number of residues.

An extent of resection threshold for seizure freedom in patients with low-grade gliomas.

OBJECTIVE Seizures are the most common presenting symptom of newly diagnosed WHO Grade II gliomas (low-grade glioma [LGG]) and significantly impair quality of life. Although gross-total resection of LGG is associated with better seizure control, it remains unclear whether an extent of resection (EOR) "threshold" exists for long-term seizure control. Specifically, what proportion of FLAIR-positive tissue in patients with newly diagnosed LGG must be removed to achieve Engel Class I seizure freedom? To clarify the EOR threshold for long-term seizure control, the authors analyzed data from a consecutive series of patients with newly diagnosed LGG who presented with seizures and subsequently underwent microsurgical resection. METHODS The authors identified consecutive patients with newly diagnosed LGG who presented with seizures and were treated at the Barrow Neurological Institute between 2002 and 2012. Patients were dichotomized into those who were seizure free postoperatively and those who were not. The EOR was calculated by quantitative comparison of pre- and postoperative MRI. Univariate analysis of these 2 groups included the chi-square test and the Mann-Whitney U-test, and a multivariate logistic regression was constructed to predict the impact of multiple independent variables on the likelihood of postoperative seizure freedom. To determine a threshold of EOR that optimizes seizure freedom, a receiver operating characteristic curve was plotted and the optimal point of discrimination was determined. RESULTS Data from 128 patients were analyzed (male/female ratio 1.37:1; mean age 40.8 years). All 128 patients presented with seizures, usually generalized (n = 57, 44.5%) or simple partial (n = 57, 44.5%). The median EOR was 90.0%. Of 128 patients, 46 (35.9%) had 100% volumetric tumor resection, 64 (50.0%) had 90%-99% volumetric tumor resection, and 11 (8.6%) had 80%-89% volumetric tumor resection. Postoperatively, 105 (82%) patients were seizure free (Engel Class I); 23 (18%) were not (Engel Classes II-IV). The proportion of seizure-free patients increased in proportion to the EOR. Predictive variables included in the regression model were preoperative Karnofsky Performance Scale score, seizure type, time from diagnosis to surgery, preoperative number of antiepileptic drugs, and EOR. Only EOR significantly affected the likelihood of postoperative Engel Class I status (OR 11.5, 95% CI 2.4-55.6; p = 0.002). The receiver operating characteristic curve generated based on Engel Class I status showed a sensitivity of 0.65 and 1 - specificity of 0.175, corresponding to an EOR of 80%. CONCLUSIONS For adult patients with LGG who suffer seizures, the results suggest that seizure freedom can be attained when EOR > 80% is achieved. Improvements in both the proportion of seizure-free patients and the durability of seizure freedom were observed beyond this 80% threshold. Interestingly, this putative EOR seizure-freedom threshold closely approximates that reported for the overall survival benefit in newly diagnosed hemispheric LGGs, suggesting that a minimum level of residual tumor burden is necessary for both disease and symptomatic progression.

Glycosylphosphatidylinositol-anchored proteins as chaperones and co-receptors for FERONIA receptor kinase signaling in Arabidopsis.

The Arabidopsis receptor kinase FERONIA (FER) is a multifunctional regulator for plant growth and reproduction. Here we report that the female gametophyte-expressed glycosylphosphatidylinositol-anchored protein (GPI-AP) LORELEI and the seedling-expressed LRE-like GPI-AP1 (LLG1) bind to the extracellular juxtamembrane region of FER and show that this interaction is pivotal for FER function. LLG1 interacts with FER in the endoplasmic reticulum and on the cell surface, and loss of LLG1 function induces cytoplasmic retention of FER, consistent with transport of FER from the endoplasmic reticulum to the plasma membrane in a complex with LLG1. We further demonstrate that LLG1 is a component of the FER-regulated RHO GTPase signaling complex and that fer and llg1 mutants display indistinguishable growth, developmental and signaling phenotypes, analogous to how lre and fer share similar reproductive defects. Together our results support LLG1/LRE acting as a chaperone and co-receptor for FER and elucidate a mechanism by which GPI-APs enable the signaling capacity of a cell surface receptor.

Porcine synapsin 1: SYN1 gene analysis and functional characterization of the promoter.

Synapsin 1 (SYN1) is a phosphoprotein involved in nerve signal transmission. The porcine SYN1 promoter orthologue was cloned and characterized to provide a means of expressing a transgene specifically in neurons. The nucleotide sequence of the promoter displayed a high degree of conservation of elements responsible for neuron-specific expression. Expression analysis of SYN1 demonstrated presence of transcript during embryonic development. Analysis of GFP expression in transgenic zebrafish embryos suggests that the pig SYN1 promoter directs expression in neuronal cells. Thus, the SYN1 promoter is a good candidate for use in the generation of pig models of human neurodegenerative disorders.