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

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

North Atlantic simulations in Coordinated Ocean-ice Reference Experiments phase II (CORE-II). Part II: Inter-annual to decadal variability

Simulated inter-annual to decadal variability and trends in the North Atlantic for the 1958-2007 period from twenty global ocean - sea-ice coupled models are presented. These simulations are performed as contributions to the second phase of the Coordinated Ocean-ice Reference Experiments (CORE-II). The study is Part II of our companion paper (Danabasoglu et al., 2014) which documented the mean states in the North Atlantic from the same models. A major focus of the present study is the representation of Atlantic meridional overturning circulation (AMOC) variability in the participating models. Relationships between AMOC variability and those of some other related variables, such as subpolar mixed layer depths, the North Atlantic Oscillation (NAO), and the Labrador Sea upper-ocean hydrographic properties, are also investigated. In general, AMOC variability shows three distinct stages. During the first stage that lasts until the mid-to late-1970s, AMOC is relatively steady, remaining lower than its long-term (1958-2007) mean. Thereafter, AMOC intensifies with maximum transports achieved in the mid-to late-1990s. This enhancement is then followed by a weakening trend until the end of our integration period. This sequence of low frequency AMOC variability is consistent with previous studies. Regarding strengthening of AMOC between about the mid-1970s and the mid-1990s, our results support a previously identified variability mechanism where AMOC intensification is connected to increased deep water formation in the subpolar North Atlantic, driven by NAO-related surface fluxes. The simulations tend to show general agreement in their temporal representations of, for example, AMOC, sea surface temperature (SST), and subpolar mixed layer depth variabilities. In particular, the observed variability of the North Atlantic SSTs is captured well by all models. These findings indicate that simulated variability and trends are primarily dictated by the atmospheric datasets which include the influence of ocean dynamics from nature superimposed onto anthropogenic effects. Despite these general agreements, there are many differences among the model solutions, particularly in the spatial structures of variability patterns. For example, the location of the maximum AMOC variability differs among the models between Northern and Southern Hemispheres. (C) 2015 Elsevier Ltd. All rights reserved