Discrete Mass Ejections from the Be/X-ray Binary A0535+26/HD245770

We present the long-term optical spectroscopic observations on the Be/X-ray binary A0535+26 from 1992 to 2010. Combining with the public V-band photometric data, we find that each giant X-ray outburst occurred in a fading phase of the optical brightness. The anti-correlation between the optical brightness and the H$\alpha$ intensity during our 2009 observations indicates a mass ejection event had taken place before the 2009 giant X-ray outburst, which might cause the formation of a low-density region in the inner part of the disk. The similar anti-correlation observed around 1996 September indicates the occurrence of the mass ejection, which might trigger the subsequent disk loss event in A0535+26.Comment: 16 pages, 5 figures. Accepted for publication in the Astrophysical Journa

Structure of Quantum Chaotic Wavefunctions: Ergodicity, Localization, and Transport

We discuss recent developments in the study of quantum wavefunctions and transport in classically ergodic systems. Surprisingly, short-time classical dynamics leaves permanent imprints on long-time and stationary quantum behavior, which are absent from the long-time classical motion. These imprints can lead to quantum behavior on single-wavelength or single-channel scales which are very different from random matrix theory expectations. Robust and quantitative predictions are obtained using semiclassical methods. Applications to wavefunction intensity statistics and to resonances in open systems are discussed.Comment: 8 pages, including 2 figures; talk given at `Dynamics of Complex Systems' workshop in Dresden, 1999 and submitted for conference proceedings to appear in Physica

A diagnosis on torque reversals in 4U 1626-67

Several X-ray pulsars have been observed to experience torque reversals, which provide important observational clues to the interaction between the neutron star magnetic field and the accretion disk. We review the current models proposed for the torque reversals and discuss their viability based on the observations of the quasi-periodic oscillations (QPOs) in 4U 1626-67. Most of these models seem to be incompatible with the evolution of the QPO frequencies if they are interpreted in terms of the beat frequency model. We suggest that winds or outflows from the neutron star and the accretion disk may play an important role in accounting for the spin-down in disk-fed neutron stars.Comment: 7 pages, accepted for publication in A&

Randomised clinical trial: a leucine-metformin-sildenafil combination (NS-0200) vs placebo in patients with non-alcoholic fatty liver disease

BACKGROUND: Sirtuin 1 (Sirt1) is suppressed in non-alcoholic fatty liver disease (NAFLD), while its' stimulation or overexpression results in reduced disease severity in pre-clinical NAFLD models. Leucine allosterically activates Sirt1 and synergise with other Sirt/AMPK/NO pathway activators. We developed a triple combination of leucine, metformin and sildenafil (NS-0200), which was effective in a mouse model of non-alcoholic steatohepatitis (NASH). AIM: To report the results from a Phase 2, randomised clinical trial of of NS-0200 in 91 subjects with NAFLD (liver fat ≥15% by magnetic resonance imaging-proton-density fat fraction (MRI-PDFF)). METHODS: Subjects were randomised to placebo, low-dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil) or high-dose NS-0200 (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) b.d. for 16 weeks; change in hepatic fat was assessed via MRI-PDFF, and lipid metabolism was assessed via changes in the lipidomic signature. Seventy subjects completed the trial and met a priori compliance criteria. Analyses were conducted on the full cohort and on those with alanine aminotransferase (ALT) values above median (50 U/L; n = 35). RESULTS: In the full cohort, active treatments did not separate from placebo. High dose NS-0200 reduced hepatic fat by 15.7% (relative change from baseline) in the high ALT group (P < 0.005) while low dose NS-0200 and placebo did not significantly change hepatic fat. Lipidomic analysis showed dose-responsive treatment effects in both overall and high ALT cohorts, with significant decreases in metabolically active lipids and up-regulation of fatty acid oxidation. CONCLUSION: These data support further evaluation of high-dose NS-0200 for treating NASH, especially in those with elevated ALT (NCT 02546609)

The Crystal Structure and RNA-Binding of an Orthomyxovirus Nucleoprotein

Genome packaging for viruses with segmented genomes is often a complex problem. This is particularly true for influenza viruses and other orthomyxoviruses, whose genome consists of multiple negative-sense RNAs encapsidated as ribonucleoprotein (RNP) complexes. To better understand the structural features of orthomyxovirus RNPs that allow them to be packaged, we determined the crystal structure of the nucleoprotein (NP) of a fish orthomyxovirus, the infectious salmon anemia virus (ISAV) (genus Isavirus). As the major protein component of the RNPs, ISAV-NP possesses a bi-lobular structure similar to the influenza virus NP. Because both RNA-free and RNA-bound ISAV NP forms stable dimers in solution, we were able to measure the NP RNA binding affinity as well as the stoichiometry using recombinant proteins and synthetic oligos. Our RNA binding analysis revealed that each ISAV-NP binds ,12 nts of RNA, shorter than the 24ﾖ28 nts originally estimated for the influenza A virus NP based on population average. The 12-nt stoichiometry was further confirmed by results from electron microscopy and dynamic light scattering. Considering that RNPs of ISAV and the influenza viruses have similar morphologies and dimensions, our findings suggest that NP-free RNA may exist on orthomyxovirus RNPs, and selective RNP packaging may be accomplished through direct RNA-RNA interactions

Btk regulates macrophage polarization in response to lipopolysaccharide

Bacterial Lipopolysaccharide (LPS) is a strong inducer of inflammation and does so by inducing polarization of macrophages to the classic inflammatory M1 population. Given the role of Btk as a critical signal transducer downstream of TLR4, we investigated its role in M1/M2 induction. In Btk deficient (Btk (−\−)) mice we observed markedly reduced recruitment of M1 macrophages following intraperitoneal administration of LPS. Ex vivo analysis demonstrated an impaired ability of Btk(−/−) macrophages to polarize into M1 macrophages, instead showing enhanced induction of immunosuppressive M2-associated markers in response to M1 polarizing stimuli, a finding accompanied by reduced phosphorylation of STAT1 and enhanced STAT6 phosphorylation. In addition to STAT activation, M1 and M2 polarizing signals modulate the expression of inflammatory genes via differential activation of transcription factors and regulatory proteins, including NF-κB and SHIP1. In keeping with a critical role for Btk in macrophage polarization, we observed reduced levels of NF-κB p65 and Akt phosphorylation, as well as reduced induction of the M1 associated marker iNOS in Btk(−/−) macrophages in response to M1 polarizing stimuli. Additionally enhanced expression of SHIP1, a key negative regulator of macrophage polarisation, was observed in Btk(−/−) macrophages in response to M2 polarizing stimuli. Employing classic models of allergic M2 inflammation, treatment of Btk (−/−) mice with either Schistosoma mansoni eggs or chitin resulted in increased recruitment of M2 macrophages and induction of M2-associated genes. This demonstrates an enhanced M2 skew in the absence of Btk, thus promoting the development of allergic inflammation

Vesicular glutamate release from central axons contributes to myelin damage

Neuronal activity can lead to vesicular release of glutamate. Here the authors demonstrate that vesicular release of glutamate occurs in axons during ischemic conditions, and that an allosteric modulator of GluN2C/D is protective in models of ischemic injury

Applications of isothermal titration calorimetry - the research and technical developments from 2011 to 2015

Isothermal titration calorimetry is a widely used biophysical technique for studying the formation or dissociation of molecular complexes. Over the last 5years, much work has been published on the interpretation of isothermal titration calorimetry (ITC) data for single binding and multiple binding sites. As over 80% of ITC papers are on macromolecules of biological origin, this interpretation is challenging. Some researchers have attempted to link the thermodynamics constants to events at the molecular level. This review highlights work carried out using binding sites characterized using x-ray crystallography techniques that allow speculation about individual bond formation and the displacement of individual water molecules during ligand binding and link these events to the thermodynamic constants for binding. The review also considers research conducted with synthetic binding partners where specific binding events like anion-π and π-π interactions were studied. The revival of assays that enable both thermodynamic and kinetic information to be collected from ITC data is highlighted. Lastly, published criticism of ITC research from a physical chemistry perspective is appraised and practical advice provided for researchers unfamiliar with thermodynamics and its interpretation

New insights into the role of motion and form vision in neurodevelopmental disorders

A selective deficit in processing the global (overall) motion, but not form, of spatially extensive objects in the visual scene is frequently associated with several neurodevelopmental disorders, including preterm birth. Existing theories that proposed to explain the origin of this visual impairment are, however, challenged by recent research. In this review, we explore alternative hypotheses for why deficits in the processing of global motion, relative to global form, might arise. We describe recent evidence that has utilised novel tasks of global motion and global form to elucidate the underlying nature of the visual deficit reported in different neurodevelopmental disorders. We also examine the role of IQ and how the sex of an individual can influence performance on these tasks, as these are factors that are associated with performance on global motion tasks, but have not been systematically controlled for in previous studies exploring visual processing in clinical populations. Finally, we suggest that a new theoretical framework is needed for visual processing in neurodevelopmental disorders and present recommendations for future research

Palladium–mediated organofluorine chemistry

Producción CientíficaThe substitution of fluorine for hydrogen in a molecule may result in profound changes in its properties and behaviour. Fluorine does not introduce special steric constraints since the F atom has a small size. However, the changes in bond polarity and the possibility of forming hydrogen bonds with other hydrogen donor fragments in the same or other molecules, may change the solubility and physical properties of the fluorinated compound when compared to the non-fluorinated one. Fluorine forms strong bonds to other elements and this ensures a good chemical stability. Altogether, fluorinated compounds are very attractive in materials chemistry and in medicinal chemistry, where many biologically active molecules and pharmaceuticals do contain fluorine in their structure and this has been shown to be essential for their activityJunta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA302U13)Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA256U13