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101.
102.
Crystal structure of the oligomerization domain of NSP4 from rotavirus reveals a core metal-binding site 总被引:6,自引:0,他引:6
Bowman GD Nodelman IM Levy O Lin SL Tian P Zamb TJ Udem SA Venkataraghavan B Schutt CE 《Journal of molecular biology》2000,304(5):861-871
During the maturation of rotaviral particles, non-structural protein 4 (NSP4) plays a critical role in the translocation of the immature capsid into the lumen of the endoplasmic reticulum. Full-length NSP4 and a 22 amino acid peptide (NSP4(114-135)) derived from this protein have been shown to induce diarrhea in young mice in an age-dependent manner, and may therefore be the agent responsible for rotavirally-induced symptoms. We have determined the crystal structure of the oligomerization domain of NSP4 which spans residues 95 to 137 (NSP4(95-137)). NSP4(95-137) self-associates into a parallel, tetrameric coiled-coil, with the hydrophobic core interrupted by three polar layers occupying a and d-heptad positions. Side-chains from two consecutive polar layers, consisting of four Gln123 and two of the four Glu120 residues, coordinate a divalent cation. Two independent structures built from MAD-phased data indicated the presence of a strontium and calcium ion bound at this site, respectively. This metal-binding site appears to play an important role in stabilizing the homo-tetramer, which has implications for the engagement of NSP4 as an enterotoxin. 相似文献
103.
1-Thio-beta-D-galactofuranosides: synthesis and evaluation as beta-D- galactofuranosidase inhibitors
Marino C; Marino K; Miletti L; Manso Alves MJ; Colli W; de Lederkremer RM 《Glycobiology》1998,8(9):901-904
Beta-D-galactofuranosidase is a good chemotherapeutic target for the design
of inhibitors, since beta-D-galactofuranose is a constituent of important
parasite glycoconjugates but is not present in the host mammals. With this
aim, we have synthesized for the first time alkyl, benzyl and aryl
1-thio-beta-D-galactofuranosides by condensation of
penta-O-benzoyl-alpha,beta-D-galactofuranose with the corresponding thiols,
in the presence of SnCl4as catalyst. The complete chemical and
spectroscopical characterization of these compounds showed that the
reaction was stereoselective. Debenzoylation with sodium methoxide afforded
the beta-S-galactofuranosides in high yield. The thioglycosides were tested
as inhibitors of the beta-D- galactofuranosidase of Penicillium fellutanum,
using for the first time 4-nitrophenyl-beta-D-galactofuranoside as
chromogenic substrate. The 4- aminophenyl-1-thio-beta-D-galactofuranoside,
obtained by catalytic hydrogenation of the nitrophenyl derivative, was the
best inhibitor being then an adequate ligand for the preparation of an
affinity phase aimed at the isolation of beta-d-galactofuranosidases from
different sources. Also the inhibitory activity of d-galactono-1, 4-lactone
was shown.
相似文献
104.
105.
106.
William D. Bowman Diana R. Nemergut Diane M. McKnight Matthew P. Miller Mark W. Williams 《Plant Ecology & Diversity》2015,8(5-6):727-738
Background: Nitrogen (N) deposition in the Front Range of the southern Rocky Mountains has been increasing for several decades, and has exceeded the critical load for several ecological metrics.Aims: Our objective was to predict potential future ecological changes in alpine zones in response to anthropogenic N deposition based on a review of research from Niwot Ridge, Colorado.Results: Empirical observations and experimental studies indicate that plant, algal and soil microbe species compositions are changing in response to N deposition, with nitrophilic species increasing in abundance. Biotic sequestration of N deposition is insufficient to compensate for greater nitrate production, leading to the potential for acidification and base cation loss.Conclusions: Changes in biotic composition in both terrestrial and aquatic ecosystems have important impacts on ecosystem functioning, including a lower capacity to take up and neutralise the acidifying effect of anthropogenic N, increasing phosphorus limitation of production in terrestrial and aquatic systems, and shifts in rates of N and carbon cycling. Continued elevated N deposition rates coupled with ongoing climate change, including warmer summer temperatures and lower snow cover of shorter duration, will influence the ecological thresholds for biotic and functional changes. We suggest that these thresholds will occur at lower inputs of N deposition under future climate change, meriting reconsideration of current N critical loads to protect sensitive alpine ecosystems. 相似文献
107.
Özgür Keleṣ Nicholas P. Barcenas Daniel H. Sprys Keith J. Bowman 《AAPS PharmSciTech》2015,16(6):1455-1464
Fracture strength of pharmaceutical compacts varies even for nominally identical samples, which directly affects compaction, comminution, and tablet dosage forms. However, the relationships between porosity and mechanical behavior of compacts are not clear. Here, the effects of porosity on fracture strength and fracture statistics of microcrystalline cellulose compacts were investigated through diametral compression tests. Weibull modulus, a key parameter in Weibull statistics, was observed to decrease with increasing porosity from 17 to 56 vol.%, based on eight sets of compacts at different porosity levels, each set containing ∼50 samples, a total of 407 tests. Normal distribution fits better to fracture data for porosity less than 20 vol.%, whereas Weibull distribution is a better fit in the limit of highest porosity. Weibull moduli from 840 unique finite element simulations of isotropic porous materials were compared to experimental Weibull moduli from this research and results on various pharmaceutical materials. Deviations from Weibull statistics are observed. The effect of porosity on fracture strength can be described by a recently proposed micromechanics-based formula.Key words: diametral compression test, finite element simulations, normal distribution, reliability, Weibull modulus 相似文献
108.
109.
Hoang H. Nguyen George F. Van Hare Michael Rudokas Tammy Bowman Jennifer N. A. Silva 《PloS one》2015,10(8)
Objectives
Smartphone-enabled ECG devices have the potential to improve patient care by enabling remote ECG assessment of patients with potential and diagnosed arrhythmias. This prospective study aimed to assess the usefulness of pediatric ECG tracings generated by the AliveCor device (Oklahoma City, OK) and to assess user satisfaction.Study Design
Enrolled pediatric patients with documented paroxysmal arrhythmia used the AliveCor device over a yearlong study period. Pediatric electrophysiologists reviewed all transmitted ECG tracings. Patient completed surveys were analyzed to assess user satisfaction.Results
35 patients were enrolled with the following diagnoses: supraventricular tachycardia (SVT, 57%), atrial fibrillation (AF, 11%), ectopic atrial tachycardia (EAT, 6%), atrial tachycardia (AT, 3%), and ventricular tachycardia (VT, 23%). A total of 238 tracings were received from 20 patients, 96% of which were of diagnostic quality for sinus rhythm, sinus tachycardia, SVT, and AF. 126 patient satisfaction surveys (64% from parents) were completed. 98% of the survey responses indicated that it was easy to obtain tracings, 93% found it easy to transmit the tracings, 98% showed added comfort in managing arrhythmia by having the device, and 93% showed interest in continued use of the device after the study period ended.Conclusions
Smartphone-enabled ECG devices can generate tracings of diagnostic quality in children. User satisfaction was extremely positive. Use of the device to manage certain patients with AF and SVT showcases the future role of remote ECGs in the successful outpatient management of arrhythmias in children by potentially reducing Emergency Department visits and healthcare costs. 相似文献110.
Rebecca Vicente-Steijn Roderick W. C. Scherptong Boudewijn P. T. Kruithof Sjoerd N. Duim Marie Jose T. H. Goumans Lambertus J. Wisse Bin Zhou William T. Pu Robert E. Poelmann Martin J. Schalij Michelle D. Tallquist Adriana C. Gittenberger-de Groot Monique RM Jongbloed 《PloS one》2015,10(9)