Secular dynamics of long-range interacting particles on a sphere in the axisymmetric limit

We investigate the secular dynamics of long-range interacting particles moving on a sphere, in the limit of an axisymmetric mean field potential. We show that this system can be described by the general kinetic equation, the inhomogeneous Balescu--Lenard equation. We use this approach to compute long-term diffusion coefficients, that are compared with direct simulations. Finally, we show how the scaling of the system's relaxation rate with the number of particles fundamentally depends on the underlying frequency profile. This clarifies why systems with a monotonic profile undergo a kinetic blocking and cannot relax as a whole under ${1/N}$ resonant effects. Because of its general form, this framework can describe the dynamics of globally coupled classical Heisenberg spins, long-range couplings in liquid crystals, or the orbital inclination evolution of stars in nearly Keplerian systems.Comment: 8 pages, 6 figures, submitted to PR

The impact of vector resonant relaxation on the evolution of binaries near a massive black hole: implications for gravitational wave sources

Binaries within the sphere of influence of a massive black hole (MBH) in galactic nuclei are susceptible to the Lidov-Kozai (LK) mechanism, which can drive orbits to high eccentricities and trigger strong interactions within the binary such as the emission of gravitational waves (GWs), and mergers of compact objects. These events are potential sources for GW detectors such as Advanced LIGO and VIRGO. The LK mechanism is only effective if the binary is highly inclined with respect to its orbit around the MBH (within a few degrees of 90 deg), implying low rates. However, close to an MBH, torques from the stellar cluster give rise to the process of vector resonant relaxation (VRR). VRR can bring a low-inclination binary into an `active' LK regime in which high eccentricities and strong interactions are triggered in the binary. Here, we study the coupled LK-VRR dynamics, with implications for LIGO and VIRGO GW sources. We carry out Monte Carlo simulations and find that the merger fraction enhancement due to LK-VRR dynamics is up to a factor of ~10 for the lower end of assumed MBH masses (M_MBH = 1e4 MSun), and decreases sharply with increasing M_MBH. We find that, even in our most optimistic scenario, the baseline BH-BH merger rate is small, and the enhancement by LK-VRR coupling is not large enough to increase the rate to well above the LIGO/VIRGO lower limit, 12 Gpc^{-3} yr^{-1}. For the Galactic Center, the LK-VRR-enhanced rate is ~100 times lower than the LIGO/VIRGO limit, and for M_MBH = 1e4 MSun, the rate barely reaches 12 Gpc^{-3} yr^{-1}.Comment: Accepted for publication in ApJ. 22 pages, 20 figure

Metabolic networking in Brunfelsia calycina petals after flower opening

Brunfelsia calycina flowers change colour from purple to white due to anthocyanin degradation, parallel to an increase in fragrance and petal size. Here it was tested whether the production of the fragrant benzenoids is dependent on induction of the shikimate pathway, or if they are formed from the anthocyanin degradation products. An extensive characterization of the events taking place in Brunfelsia flowers is presented. Anthocyanin characterization was performed using ultraperfomance liquid chromatography–quadrupole time of flight–tandem mass specrometry (UPLC-QTOF-MS/MS). Volatiles emitted were identified by headspace solid phase microextraction–gas chromatography–mass spectrometry (HS-SPME-GC-MS). Accumulated proteins were identified by 2D gel electrophoresis. Transcription profiles were characterized by cross-species hybridization of Brunfelsia cDNAs to potato cDNA microarrays. Identification of accumulated metabolites was performed by UPLC-QTOF-MS non-targeted metabolite analysis. The results include characterization of the nine main anthocyanins in Brunfelsia flowers. In addition, 146 up-regulated genes, 19 volatiles, seven proteins, and 17 metabolites that increased during anthocyanin degradation were identified. A multilevel analysis suggests induction of the shikimate pathway. This pathway is the most probable source of the phenolic acids, which in turn are precursors of both the benzenoid and lignin production pathways. The knowledge obtained is valuable for future studies on degradation of anthocyanins, formation of volatiles, and the network of secondary metabolism in Brunfelsia and related species

Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing

Women facing increased energetic demands in childhood commonly have altered adult ovarian activity and shorter reproductive lifespan, possibly comprising a strategy to optimize reproductive success. Here we sought to understand the mechanisms of early-life programming of reproductive function, by integrating analysis of reproductive tissues in an appropriate mouse model with methylation analysis of proxy tissue DNA in a well-characterized population of Bangladeshi migrants in the UK. Bangladeshi women whose childhood was in Bangladesh were found to have later pubertal onset and lower age-matched ovarian reserve than Bangladeshi women who grew-up in England. Subsequently we aimed to explore the potential relevance to the altered reproductive phenotype of one of the genes that emerged from the screens. Results: Of the genes associated with differential methylation in the Bangladeshi women whose childhood was in Bangladesh as compared to Bangladeshi women who grew up in the UK, 13 correlated with altered expression of the orthologous gene in the mouse model ovaries. These mice had delayed pubertal onset and a smaller ovarian reserve compared to controls. The most relevant of these genes for reproductive function appeared to be SRD5A1, which encodes the steroidogenic enzyme 5α reductase-1. SRD5A1 was more methylated at the same transcriptional enhancer in mice ovaries as in the women’s buccal DNA, and its expression was lower in the hypothalamus of the mice as well, suggesting a possible role in the central control of reproduction. The expression of Kiss1 and Gnrh was also lower in these mice compared to controls, and inhibition of 5α reductase-1 reduced Kiss1 and Gnrh mRNA levels and blocked GnRH release in GnRH neuronal cell cultures. Crucially, we show that inhibition of this enzyme in female mice in vivo delayed pubertal onset. Conclusions: SRD5A1/5α reductase-1 responds epigenetically to the environment and its down-regulation appears to alter the reproductive phenotype. These findings help to explain diversity in reproductive characteristics and how they are shaped by early-life environment, and reveal novel pathways that might be targeted to mitigate health issues caused by life-history trade-offs

Emerging immunopharmacological targets in multiple sclerosis.

Inflammatory demyelination of the central nervous system (CNS) is the hallmark of multiple sclerosis (MS), a chronic debilitating disease that affects more than 2.5 million individuals worldwide. It has been widely accepted, although not proven, that the major pathogenic mechanism of MS involves myelin-reactive T cell activation in the periphery and migration into the CNS, which subsequently triggers an inflammatory cascade that leads to demyelination and axonal damage. Virtually all MS medications now in use target the immune system and prevent tissue damage by modulating neuroinflammatory processes. Although current therapies such as commonly prescribed disease-modifying medications decrease the relapse rate in relapsing-remitting MS (RRMS), the prevention of long-term accumulation of deficits remains a challenge. Medications used for progressive forms of MS also have limited efficacy. The need for therapies that are effective against disease progression continues to drive the search for novel pharmacological targets. In recent years, due to a better understanding of MS immunopathogenesis, new approaches have been introduced that more specifically target autoreactive immune cells and their products, thus increasing specificity and efficacy, while reducing potential side effects such as global immunosuppression. In this review we describe several immunopharmacological targets that are currently being explored for MS therapy

Genetic markers of Restless Legs Syndrome in Parkinson disease

INTRODUCTION: Several studies proposed that Restless Legs Syndrome (RLS) and Parkinson disease (PD) may be clinically and/or etiologically related. To examine this hypothesis, we aimed to determine whether the known RLS genetic markers may be associated with PD risk, as well as with PD subtype. METHODS: Two case-control cohorts from Tel-Aviv and New-York, including 1133 PD patients and 867 controls were genotyped for four RLS-related SNPs in the genes MEIS1, BTBD9, PTPRD and MAP2K5/SKOR1. The association between genotype, PD risk and phenotype was tested using multivariate regression models. RESULTS: None of the tested SNPs was significantly associated with PD risk, neither in any individual cohort nor in the combined analysis after correction for multiple comparisons. The MAP2K5/SKOR1 marker rs12593813 was associated with higher frequency of tremor in the Tel-Aviv cohort (61.0% vs. 46.5%, p = 0.001, dominant model). However, the risk allele for tremor in this gene has been associated with reduced RLS risk. Moreover, this association did not replicate in Tremor-dominant PD patients from New-York. CONCLUSION: RLS genetic risk markers are not associated with increased PD risk or subtype in the current study. Together with previous genetic, neuropathological and epidemiologic studies, our results further strengthen the notion that RLS and PD are likely to be distinct entities