On the non-abelian Brumer-Stark conjecture and the equivariant Iwasawa main conjecture

We show that for an odd prime p, the p-primary parts of refinements of the (imprimitive) non-abelian Brumer and Brumer-Stark conjectures are implied by the equivariant Iwasawa main conjecture (EIMC) for totally real fields. Crucially, this result does not depend on the vanishing of the relevant Iwasawa mu-invariant. In combination with the authors' previous work on the EIMC, this leads to unconditional proofs of the non-abelian Brumer and Brumer-Stark conjectures in many new cases.Comment: 33 pages; to appear in Mathematische Zeitschrift; v3 many minor updates including new title; v2 some cohomological arguments simplified; v1 is a revised version of the second half of arXiv:1408.4934v

A novel metabolomic approach used for the comparison of Staphylococcus aureus planktonic cells and biofilm samples

Introduction: Bacterial cell characteristics change significantly during differentiation between planktonic and biofilm states. While established methods exist to detect and identify transcriptional and proteomic changes, metabolic fluctuations that distinguish these developmental stages have been less amenable to investigation. Objectives: The objectives of the study were to develop a robust reproducible sample preparation methodology for high throughput biofilm analysis and to determine differences between Staphylococcus aureus in planktonic and biofilm states. Methods: The method uses bead beating in a chloroform/methanol/water extraction solvent to both disrupt cells and quench metabolism. Verification of the method was performed using liquid-chromatography-mass spectrometry. Raw mass-spectrometry data was analysed using an in-house bioinformatics pipe-line incorporating XCMS, MzMatch and in-house R-scripts, with identifications matched to internal standards and metabolite data-base entries. Results: We have demonstrated a novel mechanical bead beating method that has been optimised for the extraction of the metabolome from cells of a clinical Staphylococcus aureus strain existing in a planktonic or biofilm state. This high-throughput method is fast and reproducible, allowing for direct comparison between different bacterial growth states. Significant changes in arginine biosynthesis were identified between the two cell populations. Conclusions: The method described herein represents a valuable tool in studying microbial biochemistry at a molecular level. While the methodology is generally applicable to the lysis and extraction of metabolites from Gram positive bacteria, it is particularly applicable to biofilms. Bacteria that exist as a biofilm are shown to be highly distinct metabolically from their ‘free living’ counterparts, thus highlighting the need to study microbes in different growth states. Metabolomics can successfully distinguish between a planktonic and biofilm growth state. Importantly, this study design, incorporating metabolomics, could be optimised for studying the effects of antimicrobials and drug modes of action, potentially providing explanations and mechanisms of antibiotic resistance and to help devise new antimicrobials

Probabilidade de refluxo nas veias safenas de mulheres com diferentes graus de insuficiência venosa crônica Reflux probability in saphenous veins of women with different degrees of chronic venous insufficiency

CONTEXTO: A presença de refluxo nas junções safeno-femoral e safeno-poplítea é um dado importante para programação da cirurgia de varizes. Estudos mostraram que, na maioria dos pacientes com insuficiência venosa crônica, as junções estão competentes, e o refluxo está presente ao longo do trajeto das veias safenas. OBJETIVOS: Identificar probabilidade de diferentes padrões de refluxo nas veias safenas de mulheres com vários graus de insuficiência venosa crônica e avaliar se o comprometimento das junções das safenas está associado com gravidade da insuficiência venosa. MÉTODOS: Um total de 1.184 membros inferiores de 672 mulheres foram estudados pela ultra-sonografia vascular com Doppler colorido e avaliados pela classificação clínica, etiológica, anatômica e patológica (CEAP). As extremidades foram agrupadas de acordo com a gravidade da insuficiência venosa em graus leve (CEAP C1-C2), moderado (CEAP C3) e grave (CEAP C4-C6). Para avaliar a classificação clínica CEAP na predição do padrão de refluxo, utilizou-se o Teorema de Bayers. Para avaliar associação entre classificação clínica CEAP e padrões de refluxo com ou sem comprometimento das junções das safenas, utilizou-se o teste qui-quadrado (p < 0,05). RESULTADOS: Das 1.184 extremidades avaliadas, 50,2% apresentavam varizes sem edema (CEAP C2). O padrão de refluxo segmentar foi o mais freqüente nas veias safenas magna (35,14%) e parva (8%), independente da gravidade da insuficiência venosa. As junções safeno-femoral e safeno-poplítea foram fontes de refluxo em 12 e 6% das extremidades, respectivamente. Considerando a associação entre classificação clínica CEAP e insuficiência das junções das safenas, foi observada diferença significativa entre presença de refluxo nas junções safeno-femoral (p = 0,0009) e safeno-poplítea (p = 0,0006) na doença avançada. CONCLUSÕES: O refluxo inicia-se predominantemente em segmentos no trajeto das veias safenas. As junções das safenas não são as principais fontes causadoras do refluxo no sistema venoso superficial. À medida que piora a apresentação clínica da insuficiência venosa, aumenta a probabilidade de refluxo nas junções das safenas.<br>BACKGROUND: Presence of reflux in saphenofemoral and saphenopopliteal junctions represents important data for indication of varicose vein surgery. Studies demonstrated that in most patients with chronic venous insufficiency junctions are competent and reflux is present in segments in the course of saphenous veins. OBJECTIVES: To identify the probability of different reflux patterns in the saphenous veins of women with various degrees of chronic venous insufficiency and to evaluate whether junction impairment is associated with severity of venous insufficiency. METHODS: A total of 1,184 lower limbs of 672 women were evaluated by color-flow Doppler ultrasonography and classified according to clinical, etiologic, anatomic and pathophysiological classification (CEAP). The extremities were divided according to severity of venous insufficiency into three groups: mild (CEAP C1-C2), moderate (CEAP C3) and severe (CEAP C4-C6). Bayes' theorem was used to evaluate CEAP classification as a predictor of reflux patterns. The association between CEAP clinical classification and reflux patterns with or without saphenofemoral and saphenopopliteal insufficiency was analyzed using chi-square test (p < 0.05). RESULTS: Out of 1,184 lower limbs, 50.2% had varicose veins without edema (CEAP C2). The most common reflux pattern was the segmental in both great (35.14%) and small (8%) saphenous vein, regardless of severity of venous insufficiency. Saphenofemoral and saphenopopliteal junctions were the source of reflux in 12 and 6% of lower limbs, respectively. Considering the association between CEAP clinical class and saphenous vein insufficiency, there was significant difference between presence of reflux in saphenofemoral (p = 0.0009) and saphenopopliteal (p = 0.0006) junctions in advanced disease. CONCLUSIONS: Venous reflux begins mainly in saphenous vein segments. Saphenous vein junctions are not the main sources of reflux in the superficial venous system. Risk of reflux in saphenous vein junctions increases with clinical severity of chronic venous insufficiency

A search for anomalons using plastic nuclear track detectors Paper

SIGLETIB: RO 992 (1983,14) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Submicrometer Emitter ESI Tips for Native Mass Spectrometry of Membrane Proteins in Ionic and Nonionic Detergents

Native mass spectrometry (native-MS) of membrane proteins typically requires a detergent screening protocol, protein solubilization in the preferred detergent, followed by protein liberation from the micelle by collisional activation. Here, submicrometer nano-ESI emitter tips are used for native-MS of membrane proteins solubilized in both nonionic and ionic detergent solutions. With the submicrometer nano-ESI emitter tips, resolved charge-state distributions of membrane protein ions are obtained from a 150 mM NaCl, 25 mM Tris-HCl with 1.1% octyl glucoside solution. The relative abundances of NaCl and detergent cluster ions at high m /z are significantly reduced with the submicrometer emitters compared with larger nano-ESI emitters that are commonly used. This technique is beneficial for significantly decreasing the abundances (by two to three orders of magnitude compared with the larger tip size: 1.6 μm) of detergent cluster ions formed from aqueous ammonium acetate solutions containing detergents that can overlap with the membrane protein ion signal. Resolved charge-state distributions of membrane protein ions from aqueous ammonium acetate solutions containing ionic detergents were obtained with the submicrometer nano-ESI emitters; this is the first report of native-MS of membrane proteins solubilized by ionic detergents. Graphical Abstract

Real-time HD Exchange Kinetics of Proteins from Buffered Aqueous Solution with Electrothermal Supercharging and Top-Down Tandem Mass Spectrometry

Electrothermal supercharging (ETS) with electrospray ionization produces highly charged protein ions from buffered aqueous solutions in which proteins have native folded structures. ETS increases the charge of ribonuclease A by 34% whereas only a 6% increase in charge occurs for a reduced alkylated form of this protein, which is unfolded and ~66% random coil in this solution. These results indicate that protein denaturation that occurs in the ESI droplets is the primary mechanism for ETS. ETS does not affect the extent of solution-phase hydrogen-deuterium exchange (HDX) that occurs for four proteins that have significantly different structures in solution, consistent with a droplet lifetime that is significantly shorter than observable rates of HDX. Rate constants for HDX of ubiquitin are obtained with a spatial resolution of ~1.3 residues with ETS and electron transfer dissociation of the 10+ charge-state using a single capillary containing a few μL of protein solution in which HDX continuously occurs. HDX protection at individual residues with ETS HDX is similar to that with reagent supercharging HDX and with solution phase NMR, indicating that the high spray potentials required to induce ETS do not lead to HD scrambling