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991.
von Langermann J Guterl JK Pohl M Wajant H Kragl U 《Bioprocess and biosystems engineering》2008,31(3):155-161
The application of unusual high pH-values within enzymatic cyanohydrin synthesis has been investigated. Usually enzymatic
cyanohydrin synthesis in two-phase systems requires low pH-values within the aqueous phase to suppress the non-enzymatic side
reaction. In contrast, we investigated the usage of pH-values above pH 6 by using the highly enantioselective (S)-selective hydroxynitrile lyase from Manihot esculenta. With these unusual reaction conditions also the unfavorable substrate 3-phenoxy-benzaldehyde can be converted by the wild
type enzyme with excellent conversion and enantiomeric excess yielding pure (S)-3-phenoxy-benzaldehyde cyanohydrin with an enantiomeric excess of 97%. Although the variant MeHNL–W128A shows a higher activity with respect to this reaction, the enantioselectivity was reduced (85% e.e.(S)). Additionally, a new continuous spectroscopic cyanohydrin assay monitoring the formation of 3-phenoxy-benzaldehyde cyanohydrin
was developed.
Dedicated to Prof. Dr. Christian Wandrey on the occasion of his 65th birthday. 相似文献
992.
Vorburger T Ebneter JZ Wiedenmann A Morger D Weber G Diederichs K Dimroth P von Ballmoos C 《The FEBS journal》2008,275(9):2137-2150
The rotational mechanism of ATP synthases requires a unique interface between the stator a subunit and the rotating c-ring to accommodate stability and smooth rotation simultaneously. The recently published c-ring crystal structure of the ATP synthase of Ilyobacter tartaricus represents the conformation in the absence of subunit a. However, in order to understand the dynamic structural processes during ion translocation, studies in the presence of subunit a are required. Here, by intersubunit Cys-Cys cross-linking, the relative topography of the interacting helical faces of subunits a and c from the I. tartaricus ATP synthase has been mapped. According to these data, the essential stator arginine (aR226) is located between the c-ring binding pocket and the cytoplasm. Furthermore, the spatially vicinal residues cT67C and cG68C in the isolated c-ring structure yielded largely asymmetric cross-linking products with aN230C of subunit a, suggesting a small, but significant conformational change of binding-site residues upon contact with subunit a. The conformational change was dependent on the positive charge of the stator arginine or the aR226H substitution. Energy-minimization calculations revealed possible modes for the interaction between the stator arginine and the c-ring. These biochemical results and structural restraints support a model in which the stator arginine operates as a pendulum, moving in and out of the binding pocket as the c-ring rotates along the interface with subunit a. This mechanism allows efficient interaction between subunit a and the c-ring and simultaneously allows almost frictionless movement against each other. 相似文献
993.
Ecological immunology distinguishes between the long-term evolutionary costs of possessing defences against parasites and the short-term costs of using them. Evolutionary biologists have typically focused on the former in the search for constraints on the evolution of resistance. Here, we show in the peach-potato aphid, Myzus persicae, that short-term costs may be of equal evolutionary importance. Survivors of more resistant aphid clones suffered a higher reduction of fecundity upon parasitoid attack than survivors of more susceptible clones. This genetically based trade-off between benefits and costs of defence may limit the evolution of increased resistance and explain the maintenance of genetic variation for resistance under environmental variation in parasitism risk. 相似文献
994.
Victor Kunin Jeroen Raes J Kirk Harris John R Spear Jeffrey J Walker Natalia Ivanova Christian von Mering Brad M Bebout Norman R Pace Peer Bork Philip Hugenholtz 《Molecular systems biology》2008,4(1)
To investigate the extent of genetic stratification in structured microbial communities, we compared the metagenomes of 10 successive layers of a phylogenetically complex hypersaline mat from Guerrero Negro, Mexico. We found pronounced millimeter‐scale genetic gradients that were consistent with the physicochemical profile of the mat. Despite these gradients, all layers displayed near‐identical and acid‐shifted isoelectric point profiles due to a molecular convergence of amino‐acid usage, indicating that hypersalinity enforces an overriding selective pressure on the mat community. 相似文献
995.
A protective effect of breastfeeding on overweight (binary) has been reported by meta-analyses using logistic regression, whereas studies using linear regression and BMI (continuous) detected no significant association. To assess the relationship of these differences with different outcome classification, we compared results for linear, logistic, and quantile regression models in a cross-sectional data set of considerable size. Height, weight, and questionnaire data on 9,368 preschool children were collected during school-entry examinations in 1999 and 2002 in Bavaria, Southern Germany. We calculated multivariable linear, logistic, and quantile regression models with outcomes BMI, overweight, obesity, and BMI quantiles (as appropriate). Models considered the covariates breastfeeding (breastfed vs. never breastfed), gender, age, smoking in pregnancy, TV watching, maternal BMI, parental education, and early infant weight gain. No significant association was found in the linear regression model. In the logistic model, a significant association was observed for obesity (odds ratio: 0.72 (95% confidence interval (CI) 0.55, 0.94)). In quantile regression no significant point estimates were observed for the percentiles of 0.4-0.8. However, breastfeeding reduced the BMI of children having values on the 90th and 97th percentiles by -0.23 (95% CI -0.39, -0.07) and -0.26 (95% CI -0.45, -0.07) kg/m(2), respectively, on average. In contrast, breastfeeding was significantly associated with a low shift toward higher BMI values for BMI quantiles of 0.03 and from 0.1 to 0.3. The detection of associations between breastfeeding and childhood body composition might be related to the coding of the response variable (continuous or binary) and the statistical method used (linear, logistic, or quantile regression). Quantile regression should additionally be applied in such studies. 相似文献
996.
Serpentine soil, which is naturally high in heavy metal content and has low calcium to magnesium ratios, comprises a difficult environment for most plants. An impressive number of species are endemic to serpentine, and a wide range of non-endemic plant taxa have been shown to be locally adapted to these soils. Locating genomic polymorphisms which are differentiated between serpentine and non-serpentine populations would provide candidate loci for serpentine adaptation. We have used the Arabidopsis thaliana tiling array, which has 2.85 million probes throughout the genome, to measure genetic differentiation between populations of Arabidopsis lyrata growing on granitic soils and those growing on serpentinic soils. The significant overrepresentation of genes involved in ion transport and other functions provides a starting point for investigating the molecular basis of adaptation to soil ion content, water retention, and other ecologically and economically important variables. One gene in particular, calcium-exchanger 7, appears to be an excellent candidate gene for adaptation to low CaratioMg ratio in A. lyrata. 相似文献
997.
Background
In dystrophic mdx skeletal muscle, aberrant Ca2+ homeostasis and fibre degeneration are found. The absence of dystrophin in models of Duchenne muscular dystrophy (DMD) has been connected to altered ion channel properties e.g. impaired L-type Ca2+ currents. In regenerating mdx muscle, ‘revertant’ fibres restore dystrophin expression. Their functionality involving DHPR-Ca2+-channels is elusive.Methods and Results
We developed a novel ‘in-situ’ confocal immuno-fluorescence and imaging technique that allows, for the first time, quantitative subcellular dystrophin-DHPR colocalization in individual, non-fixed, muscle fibres. Tubular DHPR signals alternated with second harmonic generation signals originating from myosin. Dystrophin-DHPR colocalization was substantial in wt fibres, but diminished in most mdx fibres. Mini-dystrophin (MinD) expressing fibres successfully restored colocalization. Interestingly, in some aged mdx fibres, colocalization was similar to wt fibres. Most mdx fibres showed very weak membrane dystrophin staining and were classified ‘mdx-like’. Some mdx fibres, however, had strong ‘wt-like’ dystrophin signals and were identified as ‘revertants’. Split mdx fibres were mostly ‘mdx-like’ and are not generally ‘revertants’. Correlations between membrane dystrophin and DHPR colocalization suggest a restored putative link in ‘revertants’. Using the two-micro-electrode-voltage clamp technique, Ca2+-current amplitudes (imax) showed very similar behaviours: reduced amplitudes in most aged mdx fibres (as seen exclusively in young mdx mice) and a few mdx fibres, most likely ‘revertants’, with amplitudes similar to wt or MinD fibres. Ca2+ current activation curves were similar in ‘wt-like’ and ‘mdx-like’ aged mdx fibres and are not the cause for the differences in current amplitudes. imax amplitudes were fully restored in MinD fibres.Conclusions
We present evidence for a direct/indirect DHPR-dystrophin interaction present in wt, MinD and ‘revertant’ mdx fibres but absent in remaining mdx fibres. Our imaging technique reliably detects single isolated ‘revertant’ fibres that could be used for subsequent physiological experiments to study mechanisms and therapy concepts in DMD. 相似文献998.
Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis 总被引:2,自引:0,他引:2
Mazroui R Di Marco S Clair E von Roretz C Tenenbaum SA Keene JD Saleh M Gallouzi IE 《The Journal of cell biology》2008,180(1):113-127
The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is significantly reduced in the absence of pp32/PHAP-I. Substituting aspartate 226 with an alanine creates a noncleavable isoform of HuR that, when overexpressed, maintains its association with pp32/PHAP-I and delays the apoptotic response. Thus, we propose a model in which HuR association with pp32/PHAP-I and its caspase-mediated cleavage constitutes a regulatory step that contributes to an amplified apoptotic response. 相似文献
999.
Liebner S Corada M Bangsow T Babbage J Taddei A Czupalla CJ Reis M Felici A Wolburg H Fruttiger M Taketo MM von Melchner H Plate KH Gerhardt H Dejana E 《The Journal of cell biology》2008,183(3):409-417
The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/β-catenin (β-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of β-cat in vivo enhances barrier maturation, whereas inactivation of β-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of β-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of β-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of β-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown. 相似文献
1000.