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231.
Jørgensen CS Trandum C Larsen N Ryder LR Gajhede M Skov LK Højrup P Barkholt V Houen G 《Protein and peptide letters》2005,12(7):687-693
The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (Tm) increased from 31 degrees C at pH 5 to 51 degrees C at pH 9, but electrophoretic analysis revealed that calreticulin oligomerized instead of unfolding. Structural analyses showed that the single C-terminal alpha-helix was of major importance to the conformational stability of calreticulin. 相似文献
232.
Nielsen EM Skov MN Madsen JJ Lodal J Jespersen JB Baggesen DL 《Applied and environmental microbiology》2004,70(11):6944-6947
Wild animals living close to cattle and pig farms (four each) were examined for verocytotoxin-producing Escherichia coli (VTEC; also known as Shiga toxin-producing E. coli). The prevalence of VTEC among the 260 samples from wild animals was generally low. However, VTEC isolates from a starling (Sturnus vulgaris) and a Norway rat (Rattus norvegicus) were identical to cattle isolates from the corresponding farms with respect to serotype, virulence profile, and pulsed-field gel electrophoresis type. This study shows that wild birds and rodents may become infected from farm animals or vice versa, suggesting a possible role in VTEC transmission. 相似文献
233.
Axel Abelein J?rn D?vling Kaspersen S?ren Bang Nielsen Grethe Vestergaard Jensen Gunna Christiansen Jan Skov Pedersen Jens Danielsson Daniel E. Otzen Astrid Gr?slund 《The Journal of biological chemistry》2013,288(32):23518-23528
Intermediate amyloidogenic states along the amyloid β peptide (Aβ) aggregation pathway have been shown to be linked to neurotoxicity. To shed more light on the different structures that may arise during Aβ aggregation, we here investigate surfactant-induced Aβ aggregation. This process leads to co-aggregates featuring a β-structure motif that is characteristic for mature amyloid-like structures. Surfactants induce secondary structure in Aβ in a concentration-dependent manner, from predominantly random coil at low surfactant concentration, via β-structure to the fully formed α-helical state at high surfactant concentration. The β-rich state is the most aggregation-prone as monitored by thioflavin T fluorescence. Small angle x-ray scattering reveals initial globular structures of surfactant-Aβ co-aggregated oligomers and formation of elongated fibrils during a slow aggregation process. Alongside this slow (minutes to hours time scale) fibrillation process, much faster dynamic exchange (kex ∼1100 s−1) takes place between free and co-aggregate-bound peptide. The two hydrophobic segments of the peptide are directly involved in the chemical exchange and interact with the hydrophobic part of the co-aggregates. Our findings suggest a model for surfactant-induced aggregation where free peptide and surfactant initially co-aggregate to dynamic globular oligomers and eventually form elongated fibrils. When interacting with β-structure promoting substances, such as surfactants, Aβ is kinetically driven toward an aggregation-prone state. 相似文献
234.
Cécile Albenne Bart A. Van Der Veen Gabrielle Potocki-Véronèse Gilles Joucla Lars Skov Osman Mirza 《Biocatalysis and Biotransformation》2013,31(4-5):271-277
Rational engineering of amylosucrase required detailed investigations of the molecular basis of catalysis. Biochemical characterization of the enzyme coupled to structural analyses enabled the polymerization mechanism to be elucidated. This provided key information for successfully changing amylosucrase to a hydrolase or an improved polymerase using site-directed mutagenesis. In parallel, a combinatorial approach was developed to further improve the catalyst. The method, based on random mutagenesis and recombination of parent sequences, has generated libraries of variants. These were searched for improved polymer formation using a first step of selection followed by a screening test including a double detection method. Several mutants with desired properties have been isolated, their sequences revealed that they could not have been designed following a rational approach. 相似文献
235.
Tina R. Elmholdt Anne B. B. Olesen Bettina J?rgensen Stinne Kvist Lone Skov Henrik S. Thomsen Peter Marckmann Michael Pedersen 《PloS one》2013,8(12)
Background
Nephrogenic systemic fibrosis is a debilitating and painful disorder with an increased stimulation of the connective tissue in the skin and systemic tissues. The disease is associated with exposure to gadolinium-based contrast agent used in magnetic resonance imaging in patients with renal impairment.Methods
The prevalence of nephrogenic systemic fibrosis has so far never been determined at a national level. In 2009, Denmark was the first country to design a guideline for the tracing of nephrogenic systemic fibrosis patients. The aim of this paper is to communicate the main findings of this quest.Results
The outcome of the nationwide investigation revealed that Denmark had 65 patients with nephrogenic systemic fibrosis and thereby the highest prevalence of nephrogenic systemic fibrosis worldwide with 65 per 5.6 million inhabitants, or 12 per million.Conclusions
The nationwide investigation in Denmark revealed the highest prevalence of NSF worldwide. This may be rooted in a high level of awareness of NSF both among doctors, politicians and, not least, the media, combined with the fact that a nationwide NSF investigation was initiated. 相似文献236.
Hans Gustav Thyregod Lars Søndergaard Nikolaj Ihlemann Olaf Franzen Lars Willy Andersen Peter Bo Hansen Peter Skov Olsen Henrik Nissen Per Winkel Christian Gluud Daniel Andreas Steinbrüchel 《Trials》2013,14(1):1-10
Background
Degenerative aortic valve (AV) stenosis is the most prevalent heart valve disease in the western world. Surgical aortic valve replacement (SAVR) has until recently been the standard of treatment for patients with severe AV stenosis. Whether transcatheter aortic valve implantation (TAVI) can be offered with improved safety and similar effectiveness in a population including low-risk patients has yet to be examined in a randomised setting.Methods/Design
This randomised clinical trial will evaluate the benefits and risks of TAVI using the transarterial CoreValve System (Medtronic Inc., Minneapolis, MN, USA) (intervention group) compared with SAVR (control group) in patients with severe degenerative AV stenosis. Randomisation ratio is 1:1, enrolling a total of 280 patients aged 70 years or older without significant coronary artery disease and with a low, moderate, or high surgical risk profile. Trial outcomes include a primary composite outcome of myocardial infarction, stroke, or all-cause mortality within the first year after intervention (expected rates 5% for TAVI, 15% for SAVR). Exploratory safety outcomes include procedure complications, valve re-intervention, and cardiovascular death, as well as cardiac, cerebral, pulmonary, renal, and vascular complications. Exploratory efficacy outcomes include New York Heart Association functional status, quality of life, and valve prosthesis and cardiac performance. Enrolment began in December 2009, and 269 patients have been enrolled up to December 2012.Discussion
The trial is designed to evaluate the performance of TAVI in comparison with SAVR. The trial results may influence the choice of treatment modality for patients with severe degenerative AV stenosis.Trial registration
ClinicalTrials.gov: NCT01057173 相似文献237.
Objectives
To evaluate therapy for Mycoplasma genitalium infection with doxycycline or azithromycin 1 g compared to five days of azithromycin (total dose 1.5 g).Methods
A retrospective case study was performed among patients attending the STD-clinic in Falun, Sweden 1998–2005. All patients with a positive PCR test for M. genitalium were routinely offered a test of cure (toc). Response to doxycycline for 9 days, azithromycin 1 g single dose and extended azithromycin (500 mg on day 1 followed by 250 mg o.d. for 4 days) was determined. In patients with treatment failure after azithromycin, macrolide resistance was monitored before and after treatment. Furthermore, the rate of macrolide resistance was monitored for positive specimens available from 2006–2011.Results
The eradication rate after doxycycline was 43% (48% for women and 38% for men), for azithromycin 1 g 91% (96% for women and 88% for men) and for extended azithromycin 99% (100% for women and 93% for men). Macrolide resistance developed in 7/7 examined (100%) of those testing positive after azithromycin 1 g, but in none of those treated with extended azithromycin. Macrolide resistance before treatment increased from 0% in 2006 and 2007 to 18% in 2011.Conclusions
These findings confirm the results from other studies showing that doxycycline is inefficient in eradicating M. genitalium. Although azithromycin 1 g was not significantly less efficient than extended dosage, it was associated with selection of macrolide resistant M. genitalium strains and should not be used as first line therapy for M. genitalium. Monitoring of M. genitalium macrolide resistance should be encouraged. 相似文献238.
239.
Using small-angle x-ray scattering, we probe the effect of histone tails on both internucleosomal interactions and nucleosome conformation. To get insight into the specific role of H3 and H4 histone tails, perfectly monodisperse recombinant nucleosome core particles were reconstituted, either intact or deprived of both H3 and H4 histone tails (gH3gH4). The main result is that H3 and H4 histone tails are necessary to induce attractive interactions between NCPs. A pair potential model was used to describe interactions between NCPs. At all salt concentrations, interactions between gH3gH4 NCPs are best described by repulsive interactions exclusively. For intact NCPs, an additional attractive term, with a 5–10 kT magnitude and 20 Å range, is required to account for interparticle interactions above 50 mM monovalent salt. Regarding conformation, intact NCPs in solution are similar to NCPs in 3D crystals. gH3gH4 NCPs instead give rise to slightly different small-angle x-ray scattering curves that can be understood as a more opened conformation of the particle, where DNA ends are slightly detached from the core. 相似文献
240.
Albenne C Skov LK Tran V Gajhede M Monsan P Remaud-Siméon M André-Leroux G 《Proteins》2007,66(1):118-126
Amylosucrase from Neisseria polysaccharea (AS) is a transglucosidase from the glycoside-hydrolase family 13 that catalyzes the synthesis of an amylose-like polymer from sucrose, without any primer. Its affinity towards glycogen is particularly noteworthy since glycogen is the best D-glucosyl unit acceptor and the most efficient activator (98-fold k(cat) increase) known for this enzyme. Glycogen-enzyme interactions were modeled starting from the crystallographic AS: maltoheptaose complex, where two key oligosaccharide binding sites, OB1 and OB2, were identified. Two maltoheptaose molecules were connected by an alpha-1,6 branch by molecular modeling to mimic a glycogen branching. Among the various docking positions obtained, four models were chosen based on geometry and energy criteria. Robotics calculations enabled us to describe a back and forth motion of a hairpin loop of the AS specific B'-domain, a movement that assists the elongation of glycogen branches. Modeling data combined with site-directed mutagenesis experiments revealed that the OB2 surface site provides an anchoring platform at the enzyme surface to capture the polymer and direct the branches towards the OB1 acceptor site for elongation. On the basis of the data obtained, a semiprocessive glycogen elongation mechanism can be proposed. 相似文献