Theoretical Analysis of the "Double-q" Magnetic Structure of CeAl2

A model involving competing short-range isotropic Heisenberg interactions is developed to explain the "double-q" magnetic structure of CeAl$_2$. For suitably chosen interactions, terms in the Landau expansion quadratic in the order parameters explain the condensation of incommensurate order at wavevectors in the star of (1/2 $-\delta$, 1/2 $+\delta$, 1/2)$(2\pi/a)$, where $a$ is the cubic lattice constant. We show that the fourth order terms in the Landau expansion lead to the formation of the so-called "double-q" magnetic structure in which long-range order develops simultaneously at two symmetry-related wavevectors, in striking agreement with the magnetic structure determinations. Based on the value of the ordering temperature and of the Curie-Weiss $\Theta$ of the susceptibility, we estimate that the nearest neighbor interaction $K_0$ is ferromagnetic, with $K_0/k=-11\pm 1$K and the next-nearest neighbor interaction $J$ is antiferromagnetic with $J/k=6 \pm 1$K. We also briefly comment on the analogous phenomenon seen in the similar system TmS.Comment: 22 pages, 6 figure

Identification of iridoid glucoside transporters in Catharanthus roseus

Monoterpenoid indole alkaloids (MIAs) are plant defense compounds and high-value pharmaceuticals. Biosynthesis of the universal MIA precursor, secologanin, is organized between internal phloem-associated parenchyma (IPAP) and epidermis cells. Transporters for intercellular transport of proposed mobile pathway intermediates have remained elusive. Screening of an Arabidopsis thaliana transporter library expressed in Xenopus oocytes identified AtNPF2.9 as a putative iridoid glucoside importer. Eight orthologs were identified in Catharanthus roseus, of which three, CrNPF2.4, CrNPF2.5 and CrNPF2.6, were capable of transporting the iridoid glucosides 7-deoxyloganic acid, loganic acid, loganin and secologanin into oocytes. Based on enzyme expression data and transporter specificity, we propose that several enzymes of the biosynthetic pathway are present in both IPAP and epidermis cells, and that the three transporters are responsible for transporting not only loganic acid, as previously proposed, but multiple intermediates. Identification of the iridoid glucoside-transporting CrNPFs is an important step toward understanding the complex orchestration of the seco-iridioid pathway

Swiss residents' speciality choices – impact of gender, personality traits, career motivation and life goals

BACKGROUND: The medical specialities chosen by doctors for their careers play an important part in the development of health-care services. This study aimed to investigate the influence of gender, personality traits, career motivation and life goal aspirations on the choice of medical speciality. METHODS: As part of a prospective cohort study of Swiss medical school graduates on career development, 522 fourth-year residents were asked in what speciality they wanted to qualify. They also assessed their career motivation and life goal aspirations. Data concerning personality traits such as sense of coherence, self-esteem, and gender role orientation were collected at the first assessment, four years earlier, in their final year of medical school. Data analyses were conducted by univariate and multivariate analyses of variance and covariance. RESULTS: In their fourth year of residency 439 (84.1%) participants had made their speciality choice. Of these, 45 (8.6%) subjects aspired to primary care, 126 (24.1%) to internal medicine, 68 (13.0%) to surgical specialities, 31 (5.9%) to gynaecology & obstetrics (G&O), 40 (7.7%) to anaesthesiology/intensive care, 44 (8.4%) to paediatrics, 25 (4.8%) to psychiatry and 60 (11.5%) to other specialities. Female residents tended to choose G&O, paediatrics, and anaesthesiology, males more often surgical specialities; the other specialities did not show gender-relevant differences of frequency distribution. Gender had the strongest significant influence on speciality choice, followed by career motivation, personality traits, and life goals. Multivariate analyses of covariance indicated that career motivation and life goals mediated the influence of personality on career choice. Personality traits were no longer significant after controlling for career motivation and life goals as covariates. The effect of gender remained significant after controlling for personality traits, career motivation and life goals. CONCLUSION: Gender had the greatest impact on speciality and career choice, but there were also two other relevant influencing factors, namely career motivation and life goals. Senior physicians mentoring junior physicians should pay special attention to these aspects. Motivational guidance throughout medical training should not only focus on the professional career but also consider the personal life goals of those being mentored

Transcription Factor NF-κB Is Transported to the Nucleus via Cytoplasmic Dynein/Dynactin Motor Complex in Hippocampal Neurons

Mikenberg I, Widera D, Kaus A, Kaltschmidt B, Kaltschmidt C. Transcription Factor NF-kappa B Is Transported to the Nucleus via Cytoplasmic Dynein/Dynactin Motor Complex in Hippocampal Neurons. PLOS ONE. 2007;2(7):e589.Background. Long-term changes in synaptic plasticity require gene transcription, indicating that signals generated at the synapse must be transported to the nucleus. Synaptic activation of hippocampal neurons is known to trigger retrograde transport of transcription factor NF-kappa B. Transcription factors of the NF-kappa B family are widely expressed in the nervous system and regulate expression of several genes involved in neuroplasticity, cell survival, learning and memory. Principal Findings. In this study, we examine the role of the dynein/dynactin motor complex in the cellular mechanism targeting and transporting activated NF-kappa B to the nucleus in response to synaptic stimulation. We demonstrate that overexpression of dynamitin, which is known to dissociate dynein from microtubules, and treatment with microtubule-disrupting drugs inhibits nuclear accumulation of NF-kappa B p65 and reduces NF-kappa B-dependent transcription activity. In this line, we show that p65 is associated with components of the dynein/dynactin complex in vivo and in vitro and that the nuclear localization sequence (NLS) within NF-kappa B p65 is essential for this binding. Conclusion. This study shows the molecular mechanism for the retrograde transport of activated NF-kappa B from distant synaptic sites towards the nucleus

Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = −0.14; 95% confidence interval [CI]: −0.24 to −0.03; p value = 0.010) and MDD (β = −0.16; 95% CI: −0.27 to −0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34–1.93; p value = 2e−7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD

MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival

MarvelD3 is a transmembrane component of tight junctions, but there is little evidence for a direct involvement in the junctional permeability barrier. Tight junctions also regulate signaling mechanisms that guide cell proliferation; however, the transmembrane components that link the junction to such signaling pathways are not well understood. In this paper, we show that MarvelD3 is a dynamic junctional regulator of the MEKK1-c-Jun NH2-terminal kinase (JNK) pathway. Loss of MarvelD3 expression in differentiating Caco-2 cells resulted in increased cell migration and proliferation, whereas reexpression in a metastatic tumor cell line inhibited migration, proliferation, and in vivo tumor formation. Expression levels of MarvelD3 inversely correlated with JNK activity, as MarvelD3 recruited MEKK1 to junctions, leading to down-regulation of JNK phosphorylation and inhibition of JNK-regulated transcriptional mechanisms. Interplay between MarvelD3 internalization and JNK activation tuned activation of MEKK1 during osmotic stress, leading to junction dissociation and cell death in MarvelD3-depleted cells. MarvelD3 thus couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival

Modelling Jets, Tori and Flares in Pulsar Wind Nebulae

In this contribution we review the recent progress in the modelling of Pulsar Wind Nebulae (PWN). We start with a brief overview of the relevant physical processes in the magnetosphere, the wind-zone and the inflated nebula bubble. Radiative signatures and particle transport processes obtained from 3D simulations of PWN are discussed in the context of optical and X-ray observations. We then proceed to consider particle acceleration in PWN and elaborate on what can be learned about the particle acceleration from the dynamical structures called GwispsG observed in the Crab nebula. We also discuss recent observational and theoretical results of gamma-ray flares and the inner knot of the Crab nebula, which had been proposed as the emission site of the flares. We extend the discussion to GeV flares from binary systems in which the pulsar wind interacts with the stellar wind from a companion star. The chapter concludes with a discussion of solved and unsolved problems posed by PWN