Evaluating nuclear proteincoding genes for phylogenetic utility in beetles.

a b s t r a c t Although nuclear protein-coding genes have proven broadly useful for phylogenetic inference, relatively few such genes are regularly employed in studies of Coleoptera, the most diverse insect order. We increase the number of loci available for beetle systematics by developing protocols for three genes previously unused in beetles (alpha-spectrin, RNA polymerase II and topoisomerase I) and by refining protocols for five genes already in use (arginine kinase, CAD, enolase, PEPCK and wingless). We evaluate the phylogenetic performance of each gene in a Bayesian framework against a presumably known test phylogeny. The test phylogeny covers 31 beetle specimens and two outgroup taxa of varying age, including three of the four extant beetle suborders and a denser sampling in Adephaga and in the carabid genus Bembidion. All eight genes perform well for Cenozoic divergences and accurately separate closely related species within Bembidion, but individual genes differ markedly in accuracy over the older Mesozoic and Permian divergences. The concatenated data reconstruct the test phylogeny with high support in both Bayesian and parsimony analyses, indicating that combining data from multiple nuclear loci will be a fruitful approach for assembling the beetle tree of life

One-zone models for spheroidal galaxies with a central supermassive black-hole. Self-regulated Bondi accretion

By means of a one-zone evolutionary model, we study the co-evolution of supermassive black holes and their host galaxies, as a function of the accretion radiative efficiency, dark matter content, and cosmological infall of gas. In particular, the radiation feedback is computed by using the self-regulated Bondi accretion. The models are characterized by strong oscillations when the galaxy is in the AGN state with a high accretion luminosity. We found that these one-zone models are able to reproduce two important phases of galaxy evolution, namely an obscured-cold phase when the bulk of star formation and black hole accretion occur, and the following quiescent hot phase in which accretion remains highly sub-Eddington. A Compton-thick phase is also found in almost all models, associated with the cold phase. An exploration of the parameter space reveals that the closest agreement with the present-day Magorrian relation is obtained, independently of the dark matter halo mass, for galaxies with a low-mass seed black hole, and the accretion radiative efficiency ~0.1.Comment: Accepted for publication in A&A, 12 pages, 5 figure

Quantumgroups in the Higgs Phase

In the Higgs phase we may be left with a residual finite symmetry group H of the condensate. The topological interactions between the magnetic- and electric excitations in these so-called discrete H gauge theories are completely described by the Hopf algebra or quantumgroup D(H). In 2+1 dimensional space time we may add a Chern-Simons term to such a model. This deforms the underlying Hopf algebra D(H) into a quasi-Hopf algebra by means of a 3-cocycle H. Consequently, the finite number of physically inequivalent discrete H gauge theories obtained in this way are labelled by the elements of the cohomology group H^3(H,U(1)). We briefly review the above results in these notes. Special attention is given to the Coulomb screening mechanism operational in the Higgs phase. This mechanism screens the Coulomb interactions, but not the Aharonov-Bohm interactions. (Invited talk given by Mark de Wild Propitius at `The III International Conference on Mathematical Physics, String Theory and Quantum Gravity', Alushta, Ukraine, June 13-24, 1993. To be published in Theor. Math. Phys.)Comment: 19 pages in Latex, ITFA-93-3

Associations between diffusion MRI microstructure and cerebrospinal fluid markers of Alzheimer's disease pathology and neurodegeneration along the Alzheimer's disease continuum

INTRODUCTION: White matter (WM) degeneration is a critical component of early Alzheimer's disease (AD) pathophysiology. Diffusion-weighted imaging (DWI) models, including diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator MRI (MAP-MRI), have the potential to identify early neurodegenerative WM changes associated with AD. METHODS: We imaged 213 (198 cognitively unimpaired) aging adults with DWI and used tract-based spatial statistics to compare 15 DWI metrics of WM microstructure to 9 cerebrospinal fluid (CSF) markers of AD pathology and neurodegeneration treated as continuous variables. RESULTS: We found widespread WM injury in AD, as indexed by robust associations between DWI metrics and CSF biomarkers. MAP-MRI had more spatially diffuse relationships with Aβ42/40 and pTau, compared with NODDI and DTI. DISCUSSION: Our results suggest that WM degeneration may be more pervasive in AD than is commonly appreciated and that innovative DWI models such as MAP-MRI may provide clinically viable biomarkers of AD-related neurodegeneration in the earliest stages of AD progression

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

No evidence for an association of plasma homocysteine levels and refractive error - Results from the population-based Gutenberg Health Study (GHS)

Purpose There is a strong association between severe hyperhomocysteinemia and myopia. Thus we studied the hypothesis that even moderately increased levels of homocysteine (Hcy) might be a potentially treatable risk factor for myopia. Methods The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany, including 15,010 participants aged between 35 and 74 at recruitment. The baseline examination was conducted from 2007-2012. Refraction was measured using autorefraction (HARK 599, Carl Zeiss AG, Jena, Germany). Hcy was measured by an immunoassay. We included only phakic participants without a history of corneal surgery or corneal laser treatment. We used linear regression models to evaluate the potential association between Hcy and refraction at baseline, and between Hcy and change in refraction between baseline and 5-year-follow-up examination. We used generalized estimating equation models to account for the correlation between fellow eyes. Results We included 13,749 participants, categorized as having no myopia (spherical equivalent > -0.75 D, 65.2%), low myopia (-0.75 D-2.75 D, 21.5%), moderate myopia (-3.00 D- 5.75 D, 9.8%) and high myopia (≤ -6

Quality of life in patients with transcatheter aortic valve implantation: an analysis from the INTERVENT project

BackgroundTranscatheter aortic valve implantation (TAVI) is a standard treatment for patients with aortic valve stenosis due to its very low mortality and complication rates. However, survival and physical integrity are not the only important factors. Quality of life (QoL) improvement is a crucial part in the evaluation of therapy success.MethodsPatients with TAVI were questioned about their QoL before, one month and one year after the intervention as part of the INTERVENT registry trial at Mainz University Medical Center. Three different questionnaires were included in the data collection (Katz ADL, EQ-5D-5l, PHQ-D).ResultsWe included 285 TAVI patients in the analysis (mean age 79.8 years, 59.4% male, mean EuroSCORE II 3.8%). 30-day mortality was 3.6%, complications of any kind occurred in 18.9% of the patients. Main finding was a significant increase in the general state of health measured on the visual analog scale by an average of 4.53 (± 23.58) points (BL to 1-month follow-up, p = 0.009) and by 5.19 (± 23.64) points (BL to 12-month follow-up, p = 0.016). There was also an improvement of depression symptoms, which was reflected in a decrease in the total value of the PHQ-D by 1.67 (± 4.75) points (BL to 12-month follow-up, p = 0.001). The evaluation of the EQ-5D-5l showed a significant improvement in mobility after one month (M = −0.41 (± 1.31), p < 0.001. Regarding the independence of the patients, no significant difference could be found. Apart from that, patients with risk factors, comorbidities or complications also benefited from the intervention despite their poor starting position.ConclusionWe could show an early benefit of QoL in TAVI patients with significant improvement in the subjective state of health and a decrease in symptoms of depression. These findings were consistent over 1 year of follow up

Spatial light modulation at the nanosecond scale with an atomically thin reflector

Techniques to mold the flow of light on subwavelength scales enable fundamentally new optical systems and device applications. The realization of programmable, active optical systems with fast, tunable components is among the outstanding challenges in the field. Here, we experimentally demonstrate a few-pixel beam steering device based on electrostatic gate control of excitons in an atomically thin semiconductor with strong light-matter interactions. By combining the high reflectivity of a MoSe$_2$ monolayer with a graphene split-gate geometry, we shape the wavefront phase profile to achieve continuously tunable beam deflection with a range of 10{\deg}, two-dimensional beam steering, and switching times down to 1.6 nanoseconds. Our approach opens the door for a new class of atomically thin optical systems, such as rapidly switchable beam arrays and quantum metasurfaces operating at their fundamental thickness limit