排序方式: 共有126条查询结果,搜索用时 31 毫秒
71.
Abhimanyu K. Singh M. álvaro Berbís Mónika Z. Ballmann Michelle Kilcoyne Margarita Menéndez Thanh H. Nguyen Lokesh Joshi F. Javier Ca?ada Jesús Jiménez-Barbero Mária Benk? Balázs Harrach Mark J. van Raaij 《PloS one》2015,10(9)
The virulent form of turkey adenovirus 3 (TAdV-3), also known as turkey hemorrhagic enteritis virus (THEV), is an economically important poultry pathogen, while the avirulent form is used as a vaccine. TAdV-3 belongs to the genus Siadenovirus. The carboxy-terminal region of its fibre does not have significant sequence similarity to any other adenovirus fibre heads of known structure. Two amino acid sequence differences between virulent and avirulent TAdV-3 map on the fibre head: where virulent TAdV-3 contains Ile354 and Thr376, avirulent TAdV-3 contains Met354 and Met376. We determined the crystal structures of the trimeric virulent and avirulent TAdV-3 fibre head domains at 2.2 Å resolution. Each monomer contains a beta-sandwich, which, surprisingly, resembles reovirus fibre head more than other adenovirus fibres, although the ABCJ-GHID topology is conserved in all. A beta-hairpin insertion in the C-strand of each trimer subunit embraces its neighbouring monomer. The avirulent and virulent TAdV-3 fibre heads are identical apart from the exact orientation of the beta-hairpin insertion. In vitro, sialyllactose was identified as a ligand by glycan microarray analysis, nuclear magnetic resonance spectroscopy, and crystallography. Its dissociation constant was measured to be in the mM range by isothermal titration calorimetry. The ligand binds to the side of the fibre head, involving amino acids Glu392, Thr419, Val420, Lys421, Asn422, and Gly423 binding to the sialic acid group. It binds slightly more strongly to the avirulent form. We propose that, in vivo, the TAdV-3 fibre may bind a sialic acid-containing cell surface component. 相似文献
72.
Kilcoyne M Moran AP Shashkov AS Senchenkova SN Ferris JA Corcoran AT Savage AV 《FEMS microbiology letters》2006,263(2):214-222
The nature of the polysaccharide molecules of the human enteric pathogen Campylobacter jejuni has been the subject of debate. Previously, C. jejuni 81116 was shown to contain two different polysaccharides, one acidic (polysaccharide A) and the other neutral (polysaccharide B), occurring in a 3 : 1 ratio, respectively. The aim of this study was to determine the molecular origin of these polysaccharides. Using a combination of centrifugation, gel permeation chromatography, chemical assays, and (1)H-NMR analysis, polysaccharide B was shown to be derived from lipopolysaccharide and polysaccharide A from capsular polysaccharide. Thus, C. jejuni 81116 produces both lipopolysaccharide-like molecules and capsular polysaccharide. 相似文献
73.
A series of fatty acid ester and ether derivatives have been chemically synthesised based on carbohydrate and non-carbohydrate polyhydroxylated scaffolds. The synthesised compounds, along with their corresponding fatty acid monoglyceride antimicrobials, were evaluated for antimicrobial activity against Staphylococcus aureus and Escherichia coli. Of the derivatives synthesised, several of the carbohydrate-based compounds have antimicrobial efficacy comparable with commercially available antimicrobials. The results suggest that the nature of the carbohydrate core plays a role in the efficacy of carbohydrate fatty acid derivatives as antimicrobials. 相似文献
74.
Francesca Lemme Aoife M. Doyle John Changalucha Aura Andreasen Kathy Baisley Kaballa Maganja Deborah Watson-Jones Saidi Kapiga Richard J. Hayes David A. Ross 《PloS one》2013,8(6)
Background
Young people are at high risk of HIV and developing appropriate prevention programmes requires an understanding of the risk factors for HIV in this age group. We investigated factors associated with HIV among participants aged 15–30 years in a 2007–8 cross-sectional survey nested within a community-randomised trial of the MEMA kwa Vijana intervention in 20 rural communities in northwest Tanzania.Methods
We analysed data for 7259(53%) males and 6476(47%) females. Using a proximate-determinant conceptual framework and conditional logistic regression, we obtained sex-specific Odds Ratios (ORs) for the association of HIV infection with socio-demographic, knowledge, behavioural and biological factors.Results
HSV-2 infection was strongly associated with HIV infection (females: adjOR 4.4, 95%CI 3.2–6.1; males: adjOR 4.2, 95%CI 2.8–6.2). Several socio-demographic factors (such as age, marital status and mobility), behavioural factors (condom use, number and type of sexual partnerships) and biological factors (blood transfusion, lifetime pregnancies, genital ulcers, Neisseria gonorrhoeae) were also associated with HIV infection. Among females, lifetime sexual partners (linear trend, p<0.001), ≥2 partners in the past year (adjOR 2.0, 95%CI 1.4–2.8), ≥2 new partners in the past year (adjOR 1.9 95%CI 1.2, 3.3) and concurrent partners in the past year (adjOR 1.6 95%CI 1.1, 2.4) were all associated with HIV infection.Conclusions
Efforts must be intensified to find effective interventions to reduce HSV-2. Effective behavioural interventions focusing on reducing the number of sexual partnerships and risk behaviour within partnerships are also needed. An increase in risky sexual behaviour may occur following marriage dissolution or when a young woman travels outside of her community and interventions addressing the needs of these subgroups of vulnerable women may be important.Trial Registration
ClinicalTrial.gov . NCT00248469相似文献75.
Julien Falk Jovana Drinjakovic Kin Mei Leung Asha Dwivedy Aoife G Regan Michael Piper Christine E Holt 《BMC developmental biology》2007,7(1):107
Background
Blastomere injection of mRNA or antisense oligonucleotides has proven effective in analyzing early gene function in Xenopus. However, functional analysis of genes involved in neuronal differentiation and axon pathfinding by this method is often hampered by earlier function of these genes during development. Therefore, fine spatio-temporal control of over-expression or knock-down approaches is required to specifically address the role of a given gene in these processes. 相似文献76.
Edwards RJ Moran N Devocelle M Kiernan A Meade G Signac W Foy M Park SD Dunne E Kenny D Shields DC 《Nature chemical biology》2007,3(2):108-112
Short synthetic oligopeptides based on regions of human proteins that encompass functional motifs are versatile reagents for understanding protein signaling and interactions. They can either mimic or inhibit the parent protein's activity and have been used in drug development. Peptide studies typically either derive peptides from a single identified protein or (at the other extreme) screen random combinatorial peptides, often without knowledge of the signaling pathways targeted. Our objective was to determine whether rational bioinformatic design of oligopeptides specifically targeted to potentially signaling-rich juxtamembrane regions could identify modulators of human platelet function. High-throughput in vitro platelet function assays of palmitylated cell-permeable oligopeptides corresponding to these regions identified many agonists and antagonists of platelet function. Many bioactive peptides were from adhesion molecules, including a specific CD226-derived inhibitor of inside-out platelet signaling. Systematic screens of this nature are highly efficient tools for discovering short signaling motifs in molecular signaling pathways. 相似文献
77.
Objective
To investigate efficacy of a contoured sandal being marketed for plantar heel pain with comparison to a flat flip-flop and contoured in-shoe insert/orthosis.Method
150 volunteers aged 50 (SD: 12) years with plantar heel pain (>4 weeks) were enrolled after responding to advertisements and eligibility determined by telephone and at first visit. Participants were randomly allocated to receive commercially available contoured sandals (n = 49), flat flip-flops (n = 50) or over the counter, pre-fabricated full-length foot orthotics (n = 51). Primary outcomes were a 15-point Global Rating of Change scale (GROC: 1 = a very great deal worse, 15 = a very great deal better), 13 to 15 representing an improvement and the 20-item Lower Extremity Function Scale (LEFS) on which participants rate 20 common weight bearing activities and activities of daily living on a 5-point scale (0 = extreme difficulty, 4 = no difficulty). Secondary outcomes were worst level of heel pain in the preceding week, and the foot and ankle ability measure. Outcomes were collected blind to allocation. Analyses were done on an intention to treat basis with 12 weeks being the primary outcome time of interest.Results
The contoured sandal was 68% more likely to report improvement in terms of GROC compared to flat flip-flop. On the LEFS the contoured sandal was 61% more likely than flat flip-flop to report improvement. The secondary outcomes in the main reflected the primary outcomes, and there were no differences between contoured sandal and shoe insert.Conclusions and Relevance
Physicians can have confidence in supporting a patient''s decision to wear contoured sandals or in-shoe orthoses as one of the first and simple strategies to manage their heel pain.Trial Registration
The Australian New Zealand Clinical Trials Registry ACTRN12612000463875 相似文献78.
79.
Szegezdi E Reis CR van der Sloot AM Natoni A O'Reilly A Reeve J Cool RH O'Dwyer M Knapper S Serrano L Quax WJ Samali A 《Journal of cellular and molecular medicine》2011,15(10):2216-2231
Despite progress in the treatment of acute myelogenous leukaemia (AML) the outcome often remains poor. Tumour necrosis factor related apoptosis-inducing ligand (TRAIL) is a promising therapeutic agent in many different types of tumours, but AML cells are relatively insensitive to TRAIL-induced apoptosis. Here we show that TRAIL-induced apoptosis in AML cells is predominantly mediated by death receptor 4 (DR4) and not DR5. Therefore, we constructed a variant of TRAIL (rhTRAIL-C3) that is a strong inducer of DR4-mediated apoptosis. TRAIL-C3 demonstrated much stronger pro-apoptotic activity than wild-type (WT) TRAIL in a panel of AML cell lines as well as in primary AML blasts. The higher pro-apoptotic potential was further enhanced when the TRAIL mutant was used in combination with BMS-345541, a selective inhibitor of inhibitor-κB kinases. It illustrates that combination of this TRAIL variant with chemotherapeutics or other targeted agents can kill AML with high efficacy. This may represent a major advantage over the currently used therapies that have serious toxic side effects. The high efficacy of rhTRAIL-C3 containing therapies may enable the use of lower drug doses to reduce the toxic side effects and improve patient outcome. Our findings suggest that the rational design of TRAIL variants that target DR4 potentiate the death-inducing activity of TRAIL and offer a novel therapeutic strategy for the treatment of AML. 相似文献
80.
Doyle AM Weiss HA Maganja K Kapiga S McCormack S Watson-Jones D Changalucha J Hayes RJ Ross DA 《PloS one》2011,6(9):e24866