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1.
This study presents direct experimental evidence for assessing the electrostatic and non-electrostatic contributions of proteoglycans to the compressive equilibrium modulus of bovine articular cartilage. Immature and mature bovine cartilage samples were tested in unconfined compression and their depth-dependent equilibrium compressive modulus was determined using strain measurements with digital image correlation analysis. The electrostatic contribution was assessed by testing samples in isotonic and hypertonic saline; the combined contribution was assessed by testing untreated and proteoglycan-depleted samples.Though it is well recognized that proteoglycans contribute significantly to the compressive stiffness of cartilage, results demonstrate that the combined electrostatic and non-electrostatic contributions may add up to more than 98% of the modulus, a magnitude not previously appreciated. Of this contribution, about two thirds arises from electrostatic effects. The compressive modulus of the proteoglycan-depleted cartilage matrix may be as low as 3 kPa, representing less than 2% of the normal tissue modulus; experimental evidence also confirms that the collagen matrix in digested cartilage may buckle under compressive strains, resulting in crimping patterns. Thus, it is reasonable to model the collagen as a fibrillar matrix that can sustain only tension. This study also demonstrates that residual stresses in cartilage do not arise exclusively from proteoglycans, since cartilage remains curled relative to its in situ geometry even after proteoglycan depletion. These increased insights on the structure–function relationships of cartilage can lead to improved constitutive models and a better understanding of the response of cartilage to physiological loading conditions. 相似文献
2.
Hofstetter CP Burkhardt JK Shin BJ Gürsel DB Mubita L Gorrepati R Brennan C Holland EC Boockvar JA 《PloS one》2012,7(1):e30059
Purpose
The hypoxic microenvironment of glioblastoma multiforme (GBM) is thought to increase resistance to cancer therapies. Recent evidence suggests that hypoxia induces protein phosphatase 2A (PP2A), a regulator of cell cycle and cell death. The effects of PP2A on GBM tumor cell proliferation and survival during hypoxic conditions have not been studied.Experimental Design
Expression of PP2A subunits and HIF-α proteins was measured in 65 high-grade astrocytoma and 18 non-neoplastic surgical brain specimens by western blotting. PP2A activity was measured by an immunoprecipitation assay. For in vitro experiments, GBM-derived tumor stem cell-like cells (TSCs) were exposed to severe hypoxia produced by either CoCl2 or 1% O2. PP2A activity was inhibited either by okadaic acid or by shRNA depletion of the PP2A C subunit. Effects of PP2A activity on cell cycle progression and cell survival during hypoxic conditions were assessed using flow cytometry.Results
In our patient cohort, PP2A activity was positively correlated with HIF-1∝ protein expression (P = 0.002). Patients with PP2A activity levels above 160 pMP had significantly worse survival compared to patients with levels below this threshold (P = 0.002). PP2A activity was an independent predictor of survival on multivariable analysis (P = 0.009). In our in vitro experiments, we confirmed that severe hypoxia induces PP2A activity in TSCs 6 hours after onset of exposure. PP2A activity mediated G1/S phase growth inhibition and reduced cellular ATP consumption in hypoxic TSCs. Conversely, inhibition of PP2A activity led to increased cell proliferation, exhaustion of intracellular ATP, and accelerated P53-independent cell death of hypoxic TSCs.Conclusions
Our results suggest that PP2A activity predicts poor survival in GBM. PP2A appears to reduce the metabolic demand of hypoxic TSCs and enhances tumor cell survival. Modulation of PP2A may be a potential target for cancer therapy. 相似文献3.
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
4.
Biao Zhang Camélia Matei Ghimbeu Christel Laberty Cathie Vix‐Guterl Jean‐Marie Tarascon 《Liver Transplantation》2016,6(1)
Hard carbons are considered among the most promising anode materials for Na‐ion batteries. Understanding their structure is of great importance for optimizing their Na storage capabilities and therefore achieving high performance. Herein, carbon nanofibers (CNFs) are prepared by electrospinning and their microstructure, texture, and surface functionality are tailored through carbonization at various temperatures ranging from 650 to 2800 °C. Stepwise carbonization gradually removes the heteroatoms and increases the graphitization degree, enabling us to monitor the corresponding electrochemical performance for establishing a correlation between the CNFs characteristics and Na storage behavior. Outstandingly, it is found that for CNFs carbonized at above 2000 °C, a single voltage Na uptake plateau at ≈0.1 V with a capacity of ≈200 mAh g‐1. This specific performance may be nested in the higher degree of graphitization, lower active surface area, and different porous texture of the CNFs at such temperatures. It is demonstrated via the assembly of a CNF/Na2Fe2(SO4)3 cell the benefit of such CNFs electrode for enhancing the energy density of full Na‐ion cells. This finding sheds new insights in the quest for high performance carbon based anode materials. 相似文献
5.
The aldehyde dehydrogenase from Thermoplasma acidophilum, which was previously implemented as a key enzyme in a synthetic cell-free reaction cascade for the production of alcohols, was optimized by directed evolution. Improvements have been made to enhance reaction velocity and solubility. Using a random approach followed by site-directed and saturation mutagenesis, three beneficial amino acid mutations were found after screening of ca. 20,000 variants. Mutation Y399C enhanced the protein solubility after recombinant expression in Escherichia coli 6-fold. Two further mutations, F34M and S405N, enhanced enzyme activity with the cofactor NAD+ by a factor of eight. Impacts on enzyme stability and substrate specificity were negligible. 相似文献
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7.
Marian Christoph Neidert Michael Sprenger Heini Wernli Jan-Karl Burkhardt Niklaus Krayenbühl Oliver Bozinov Luca Regli Christoph Michael Woernle 《PloS one》2013,8(12)
Objective
To assess the potential meteorological influence on the incidence of aneurysmal subarachnoid hemorrhage (SAH). Previous studies used inhomogeneous patient groups, insufficient study periods or inappropriate statistics.Patients and Methods
We analyzed 511 SAH admissions between 2004 and 2012 for which aneurysmal rupture occurred within the Zurich region. The hourly meteorological parameters considered are: surface pressure, 2-m temperature, relative humidity and wind gusts, sunshine, and precipitation. For all parameters we investigate three complementary statistical measures: i) the time evolution from 5 days before to 5 days after the SAH occurrence; ii) the deviation from the 10-year monthly mean; and iii) the change relative to the parameter''s value two days before SAH occurrence. The statistical significance of the results is determined using a Monte Carlo simulation combined with a re-sampling technique (1000×).Results
Regarding the meteorological parameters considered, no statistically significant signal could be found. The distributions of deviations relative to the climatology and of the changes during the two days prior to SAH events agree with the distributions for the randomly chosen days. The analysis was repeated separately for winter and summer to exclude compensating effects between the seasons.Conclusion
By using high-quality meteorological data analyzed with a sophisticated and robust statistical method no clearly identifiable meteorological influence for the SAH events considered can be found. Further studies on the influence of the investigated parameters on SAH incidence seem redundant. 相似文献8.
Guterl KA Haggart CR Janssen PM Holmes JW 《American journal of physiology. Heart and circulatory physiology》2007,293(6):H3707-H3712
The hypothesis that elevated systolic stress induces myocyte thickening has been difficult to test directly. We tested this hypothesis in working rat right ventricular papillary muscles using a recently developed technique for long-term muscle culture. Muscles were cultured for 36 h either isometrically at different levels of systolic stress or at physiological amounts and rates of shortening. Isometric contraction induced rapid increases in myocyte diameter regardless of the level of systolic stress, whereas control myocyte dimensions were maintained if physiological amounts and rates of systolic shortening were imposed. Myocyte thickening was accompanied by a significant decrease in cell length and number of sarcomeres in series along the long axis of the myocyte, suggesting that thickening may have occurred in part by rearrangement of existing sarcomeres. We conclude that the pattern of systolic shortening and/or diastolic lengthening regulates myocyte shape in working rat right ventricular papillary muscles, whereas systolic stress plays little or no role. 相似文献
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10.
Devina Purmessur Clare C Guterl Samuel K Cho Marisa C Cornejo Ying W Lam Bryan A Ballif Damien M Laudier James C Iatridis 《Arthritis research & therapy》2013,15(5):R122